A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.
The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A serine endopeptidase that has specificity for cleavage at ARGININE. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN, proluteinizing-hormone-releasing hormone, proenkephalins, prodynorphin, and PROINSULIN.
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.
A CALCIUM-dependent endopeptidase that has specificity for cleavage at ARGININE that is near paired basic residues. It cleaves a variety of prohormones including PRO-OPIOMELANOCORTIN; PRORENIN; proenkephalins; prodynorphin; prosomatostatin; and PROINSULIN.
Antibodies specific to INSULIN.
A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.
A family of SERINE ENDOPEPTIDASES isolated from Bacillus subtilis. EC 3.4.21.-
Proteolytic enzymes that are involved in the conversion of protein precursors such as peptide prohormones into PEPTIDE HORMONES. Some are ENDOPEPTIDASES, some are EXOPEPTIDASES.
Condensed areas of cellular material that may be bounded by a membrane.
Stable iodine atoms that have the same atomic number as the element iodine, but differ in atomic weight. I-127 is the only naturally occurring stable iodine isotope.
A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Form of radioimmunoassay in which excess specific labeled antibody is added directly to the test antigen being measured.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
An important intermediate in lipid biosynthesis and in glycolysis.
A ZINC-dependent carboxypeptidase primary found in the DIGESTIVE SYSTEM. The enzyme catalyzes the preferential cleavage of a C-terminal peptidyl-L-lysine or arginine. It was formerly classified as EC 3.4.2.2 and EC 3.4.12.3.
An oily liquid extracted from the seeds of the safflower, Carthamus tinctorius. It is used as a dietary supplement in the management of HYPERCHOLESTEROLEMIA. It is used also in cooking, as a salad oil, and as a vehicle for medicines, paints, varnishes, etc. (Dorland, 28th ed & Random House Unabridged Dictionary, 2d ed)
A plant genus of the family ASTERACEAE. Oil from the seed (SAFFLOWER OIL) is an important food oil of commerce.
An individual's objective and insightful awareness of the feelings and behavior of another person. It should be distinguished from sympathy, which is usually nonobjective and noncritical. It includes caring, which is the demonstration of an awareness of and a concern for the good of others. (From Bioethics Thesaurus, 1992)
Time period from 1901 through 2000 of the common era.
A plant genus of the family APIACEAE. The seed is used in SPICES.
Oils derived from plants or plant products.
An autosomal recessive neurodegenerative disorder caused by the absence or deficiency of BETA-GALACTOSIDASE. It is characterized by intralysosomal accumulation of G(M1) GANGLIOSIDE and oligosaccharides, primarily in neurons of the central nervous system. The infantile form is characterized by MUSCLE HYPOTONIA, poor psychomotor development, HIRSUTISM, hepatosplenomegaly, and facial abnormalities. The juvenile form features HYPERACUSIS; SEIZURES; and psychomotor retardation. The adult form features progressive DEMENTIA; ATAXIA; and MUSCLE SPASTICITY. (From Menkes, Textbook of Child Neurology, 5th ed, pp96-7)
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
Antibodies produced by a single clone of cells.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
A ubiquitously-expressed cysteine protease that plays an enzymatic role in POST-TRANSLATIONAL PROTEIN PROCESSING of proteins within SECRETORY GRANULES.
The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.
The study of natural phenomena by observation, measurement, and experimentation.
Instructional use of examples or cases to teach using problem-solving skills and critical thinking.
A course of study offered by an educational institution.
A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.
Nucleosides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)
A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.
A pituitary adenoma which secretes ADRENOCORTICOTROPIN, leading to CUSHING DISEASE.
Anterior pituitary cells that produce ADRENOCORTICOTROPHIC HORMONE.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus. (1/664)

Previously we demonstrated the expression of the long form of the leptin receptor in rodent pancreatic beta-cells and an inhibition of insulin secretion by leptin via activation of ATP-sensitive potassium channels. Here we examine pancreatic islets isolated from pancreata of human donors for their responses to leptin. The presence of leptin receptors on islet beta-cells was demonstrated by double fluorescence confocal microscopy after binding of a fluorescent derivative of human leptin (Cy3-leptin). Leptin (6.25 nM) suppressed insulin secretion of normal islets by 20% at 5.6 mM glucose. Intracellular calcium responses to 16.7 mM glucose were rapidly reduced by leptin. Proinsulin messenger ribonucleic acid expression in islets was inhibited by leptin at 11.1 mM, but not at 5.6 mM glucose. Leptin also reduced proinsulin messenger ribonucleic acid levels that were increased in islets by treatment with 10 nM glucagon-like peptide-1 in the presence of either 5.6 or 11.1 mM glucose. These findings demonstrate direct suppressive effects of leptin on insulin-producing beta-cells in human islets at the levels of both stimulus-secretion coupling and gene expression. The findings also further indicate the existence of an adipoinsular axis in humans in which insulin stimulates leptin production in adipocytes and leptin inhibits the production of insulin in beta-cells. We suggest that dysregulation of the adipoinsular axis in obese individuals due to defective leptin reception by beta-cells may result in chronic hyperinsulinemia and may contribute to the pathogenesis of adipogenic diabetes.  (+info)

Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a large population with different states of glucose tolerance. The Insulin Resistance Atherosclerosis Study (IRAS). (2/664)

Hyperinsulinemia is associated with the development of coronary heart disease. However, the underlying mechanisms are still poorly understood. Hypercoagulability and impaired fibrinolysis are possible candidates linking hyperinsulinism with atherosclerotic disease, and it has been suggested that proinsulin rather than insulin is the crucial pathophysiological agent. The aim of this study was to investigate the relationship of insulin and its precursors to markers of coagulation and fibrinolysis in a large triethnic population. A strong and independent relationship between plasminogen activator inhibitor-1 (PAI-1) antigen and insulin and its precursors (proinsulin, 32-33 split proinsulin) was found consistently across varying states of glucose tolerance (PAI-1 versus fasting insulin [proinsulin], r=0.38 [r=0.34] in normal glucose tolerance; r=0.42 [r=0.43] in impaired glucose tolerance; and r=0.38 [r=0.26] in type 2 diabetes; all P<0.001). The relationship remained highly significant even after accounting for insulin sensitivity as measured by a frequently sampled intravenous glucose tolerance test. In a stepwise multiple regression model after adjusting for age, sex, ethnicity, and clinic, both insulin and its precursors were significantly associated with PAI-1 levels. The relationship between fibrinogen and insulin and its precursors was significant in the overall population (r=0.20 for insulin and proinsulin; each P<0.001) but showed a more inconsistent pattern in subgroup analysis and after adjustments for demographic and metabolic variables. Stepwise multiple regression analysis showed that proinsulin (split products) but not fasting insulin significantly contributed to fibrinogen levels after adjustment for age, sex, clinic, and ethnicity. Decreased insulin sensitivity was independently associated with higher PAI-1 and fibrinogen levels. In summary, we were able to demonstrate an independent relationship of 2 crucial factors of hemostasis, fibrinogen and PAI-1, to insulin and its precursors. These findings may have important clinical implications in the risk assessment and prevention of macrovascular disease, not only in patients with overt diabetes but also in nondiabetic subjects who are hyperinsulinemic.  (+info)

Intact proinsulin and beta-cell function in lean and obese subjects with and without type 2 diabetes. (3/664)

OBJECTIVE: Type 2 diabetes is a heterogeneous disease in which both beta-cell dysfunction and insulin resistance are pathogenetic factors. Disproportionate hyperproinsulinemia (elevated proinsulin/insulin) is another abnormality in type 2 diabetes whose mechanism is unknown. Increased demand due to obesity and/or insulin resistance may result in secretion of immature beta-cell granules with a higher content of intact proinsulin. RESEARCH DESIGN AND METHODS: We investigated the impact of obesity on beta-cell secretion in normal subjects and in type 2 diabetic patients by measuring intact proinsulin, total proinsulin immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by specific enzyme-linked immunosorbent assays in the fasting state and during a 120-min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and obese (30.1 +/- 0.4 kg/m2) (OD) type 2 diabetic patients matched for fasting glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI-matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal control subjects. RESULTS: Diabetic patients (LD vs. LC and OD vs. OC) had elevated fasting levels of intact proinsulin 6.6 +/- 1.0 vs. 1.6 +/- 0.3 pmol/l and 7.7 +/- 2.0 vs. 1.2 +/- 0.2 pmol/l; PIM: 19.9 +/- 2.5 vs. 5.4 +/- 1.0 pmol/l and 29.6 +/- 6.1 vs. 6.1 +/- 0.9 pmol/l; and total PIM/intact insulin: 39 +/- 4 vs. 15 +/- 2% and 35 +/- 5 vs. 13 +/- 2%, all P < 0.01. After glucagon stimulation, PIM levels were disproportionately elevated (PIM/intact insulin based on area under the curve analysis) in diabetic patients (LD vs. LC and OD vs. OC): 32.6 +/- 6.7 vs. 9.2 +/- 1.1% and 22.7 +/- 5.2 vs. 9.1 +/- 1.1%, both P < 0.05. Intact insulin and C-peptide net responses were significantly reduced in type 2 diabetic patients, most pronounced in the lean group. The ratio of intact proinsulin to PIM was higher in diabetic patients after stimulation in both LD versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both P < 0.01. In obese normal subjects, intact proinsulin/PIM was lower both in the fasting state and after glucagon stimulation: OC versus LC: 22 +/- 3 vs. 33 +/- 3% (fasting) and 16 +/- 2 vs. 23 +/- 2% (stimulated), both P < 0.05. CONCLUSIONS: Increased secretory demand from obesity-associated insulin resistance cannot explain elevated intact proinsulin and disproportionate hyperproinsulinemia in type 2 diabetes. This abnormality may be an integrated part of pancreatic beta-cell dysfunction in this disease.  (+info)

Adenovirus-mediated overexpression of uncoupling protein-2 in pancreatic islets of Zucker diabetic rats increases oxidative activity and improves beta-cell function. (4/664)

The discovery of uncoupling protein (UCP)-2, a ubiquitously expressed protein homologous to UCP-1, has raised the possibility that energy balance of cells might be regulated in tissues other than brown adipocytes. In normal pancreatic islets, UCP-2 is upregulated by leptin and is low in leptin-resistant islets of ZDF rats. To determine whether UCP-2 does, in fact, have uncoupling activity and, if so, whether such activity would favorably influence the abnormalities in leptin-unresponsive UCP-2-underexpressing islets of diabetic ZDF rats, we transferred the UCP-2 gene to the islets of diabetic ZDF rats and lean (+/+) ZDF control rats. Although ATP was reduced by 23% in both groups of islets, the ATP:ADP ratio increased by 42 and 141%, respectively. [3H]palmitate oxidation was increased by 50%, and [3H]glucose oxidation was 42-63% higher. Preproinsulin mRNA was 2.9-fold above control levels, and glucose-stimulated insulin secretion, which was negligible in control ZDF rat islets, was improved in UCP-2-overexpressing islets. The high fat content of the islets was not reduced, however. We conclude that UCP-2 has uncoupling function when overexpressed in leptin-insensitive islets and that its overexpression corrects the underexpression of the insulin gene and ameliorates glucose-stimulated insulin secretion, possibly by increasing the ATP:ADP ratio.  (+info)

Fasting proinsulin concentrations predict the development of type 2 diabetes. (5/664)

OBJECTIVE: The development of specific assays allows the different molecules in the proinsulin processing pathway to be measured separately. 32,33 Split proinsulin is the predominant form of proinsulin and accounts for the disproportionate hyperproinsulinemia seen in individuals with prevalent type 2 diabetes. This study was established to examine whether the concentration of this molecule predicts diabetes. RESEARCH DESIGN AND METHODS: A population-based longitudinal cohort study was conducted in Ely, Cambridgeshire. At baseline, 1,122 individuals completed a 75-g oral glucose tolerance test (OGTT). At the 4.5-year follow-up study, repeat OGTTs were performed on 937 of the cohort of 1,071 individuals who had been nondiabetic at baseline. RESULTS: A total of 26 people progressed to diabetes as determined by the OGTTs. The risk of progression was strongly related to the fasting glucose concentration (relative risk [RR] comparing top with bottom quartile 17.6 [95% CI 2.4-130.4]) and fasting 32,33 split proinsulin (RR 16.4 [2.2-121.9]), but less strongly to the fasting insulin (RR 4.41 [1.5-12.9]) or intact proinsulin (RR 5.2 [1.5-17.3]). In multivariate analyses, these associations were independent of age, sex, BMI, and baseline glucose tolerance category. Subjects in the top quartile for fasting glucose and total proinsulin with a family history of diabetes were a high-risk subgroup (incidence 65.8 per 1,000 person-years of follow-up [pyfu]); 30% of them progressed to diabetes at follow-up. CONCLUSIONS: Fasting 32,33 split proinsulin independently predicts the development of diabetes. This prediction was better than that observed for either the insulin or intact proinsulin concentrations. The combination of family history, fasting glucose, and total proinsulin identified a subgroup of individuals at high risk of progression who might benefit from targeted interventions.  (+info)

Cellular immune responses against proinsulin: no evidence for enhanced reactivity in individuals with IDDM. (6/664)

Investigations of humans and nonobese diabetic mice suggest that proinsulin and/or a fragment of the region spanning C-peptide and the B-chain of insulin (i.e., proinsulin peptide) may serve as key autoantigens in IDDM. Therefore, we analyzed cellular immune reactivities against these molecules in people with or at varying risks for the disease to clarify their role in the pathogenesis of IDDM. In vitro peripheral blood mononuclear cell (PBMC) responses against these antigens, a control antigen (tetanus toxoid), and phytohemaglutinin were determined in 60 individuals with newly diagnosed IDDM (< or = 1 day from diagnosis) in 34 islet cell cytoplasmic autoantibody- and/or insulin autoantibody-negative first-degree relatives of the IDDM subjects, and in 28 autoantibody-negative control subjects. Unlike previous reports suggesting diabetes-associated elevations in cellular immunity to other beta-cell antigens (e.g., GAD, IA-2, etc.), we observed equivalent levels of phytohemaglutinin stimulation and cellular proliferation in all groups against these antigens (all P values were not significant). The mean stimulation index +/- SD and frequency of reactivity to proinsulin for healthy control subjects and IDDM patients, respectively, were as follows: 1 microg/ml (1.5 +/- 1.0, 1 out of 17 [6%]; 1.9 +/- 1.4, 4 out of 33 [12%]); 10 microg/ml (1.7 +/- 1.3, 1 out of 17 [6%]; 1.2 +/- 0.6, 0 out of 28 [0%]); and 50 microg/ml (1.2 +/- 0.6, 1 out of 16 [6%]; 1.1 +/- 0.6, 1 out of 27 [4%]). The response in healthy control subjects, autoantibody-negative relatives, and IDDM patients, respectively, against the proinsulin peptide fragment were as follows: 1 microg/ml (0.9 +/- 0.4, 1 out of 12 [8%]; 1.3 +/- 1.1, 4 out of 34 [11%]; 1.1 +/- 0.3, 2 out of 28 [7%]); 10 microg/ml (0.9 +/- 0.6, 1 out of 12 [8%]; 1.2 +/- 0.6, 3 out of 34 [9%] 1.4 +/- 1.7, 2 out of 28 [7%]); and 50 microg/ml (1.0 +/- 0.7, 1 out of 12 [8%]; 1.2 +/- 0.5, 2 out of 34 [6%]; 1.3 +/- 0.5, 2 out of 28 [7%]). Taken together with previous studies reporting relatively infrequent occurrences of autoantibodies to proinsulin, the role of immunity to this molecule in the pathogenesis of IDDM in humans remains unclear.  (+info)

Impaired beta-cell functions induced by chronic exposure of cultured human pancreatic islets to high glucose. (7/664)

In type 2 diabetes, chronic hyperglycemia has been suggested to be detrimental to beta-cell function, causing reduced glucose-stimulated insulin secretion and disproportionately elevated proinsulin. In the present study, we investigated the effect on several beta-cell functions of prolonged in vitro exposure of human pancreatic islet cultures to high glucose concentrations. Islets exposed to high glucose levels (33 mmol/l) for 4 and 9 days showed dramatic decreases in glucose-induced insulin release and in islet insulin content, with increased proportion of proinsulin-like peptides relative to insulin. The depletion in insulin stores correlated with the reduction in insulin mRNA levels and human insulin promoter transcriptional activity. We also demonstrated that high glucose dramatically lowered the binding activity of pancreatic duodenal homeobox 1 (the glucose-sensitive transcription factor), whereas the transcription factor rat insulin promoter element 3b1 activator was less influenced and insulin enhancer factor 1 remained unaffected. Most of these beta-cell impairments were partially reversible when islets first incubated for 6 days in high glucose were transferred to normal glucose (5.5 mmol/l) concentrations for 3 days. We conclude that cultured human islets are sensitive to the deleterious effect of high glucose concentrations at multiple functional levels, and that such mechanisms may play an important role in the decreased insulin production and secretion of type 2 diabetic patients.  (+info)

Insulin secretion: feed-forward control of insulin biosynthesis? (8/664)

It has long been accepted wisdom that insulin secreted from islet beta cells has either no effect, or an inhibitory feedback effect, on insulin synthesis and secretion. Recent work suggests, instead, that secreted insulin acts directly on beta cells, via its own receptor, to enhance insulin production in an autocrine feed-forward loop.  (+info)

TY - JOUR. T1 - Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes. T2 - The Insulin Resistance Atherosclerosis Study (IRAS). AU - Loopstra-Masters, R. C.. AU - Haffner, S. M.. AU - Lorenzo, C.. AU - Wagenknecht, L. E.. AU - Hanley, A. J.. PY - 2011/12/1. Y1 - 2011/12/1. N2 - Aims: Associations of proinsulin-to-insulin ratios with incident type 2 diabetes have been inconsistent. The use of C-peptide as the denominator in the ratio may allow for better prediction because C-peptide concentration is not affected by hepatic insulin clearance. The objective of this paper was to compare fasting intact and split proinsulin-to-insulin ratios (PI/I, SPI/I) with intact and split proinsulin-to-C-peptide ratios (PI/C-pep, SPI/C-pep) in the prediction of type 2 diabetes. Methods: Prospective data on 818 multi-ethnic adults without diabetes at baseline from the Insulin Resistance Atherosclerosis Study (IRAS) were used. Insulin sensitivity (S I) and acute ...
Insulin responses and insulin levels seem to decline with age. However, the question of beta cell impairment attributable to ageing has been sparsely addressed in population-based studies. Non-fasting insulin levels are determined by the ambient degree of insulin resistance together with the capacity of beta cells to compensate by insulin secretion to prevent hyperglycaemia. A raised proinsulin-to-insulin ratio (proinsulin/insulin) due to impaired processing of proinsulin is an early marker of beta cell dysfunction. We hypothesised that in a general population, signs of beta cell failure with advancing age manifest not only by decreases in random insulin, but also with a corresponding increase in its precursor proinsulin. In the Tromsø Study 1994-95 we measured insulin and proinsulin concentrations in random blood samples from 6212 persons without self-reported diabetes mellitus and plotted the levels as percentiles according to age. In regression analyses we assessed the relationships between age and
The actions of thyroid hormone (TH) on pancreatic beta cells have not been thoroughly explored, with current knowledge being limited to the modulation of insulin secretion in response to glucose, and beta cell viability by regulation of pro-mitotic and pro-apoptotic factors. Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression, b) proinsulin transcripts and eEF1A protein binding to the actin cytoskeleton, c) actin cytoskeleton arrangement, and d) proinsulin mRNA poly(A) tail length modulation in INS-1E cells cultured in different media containing: i) normal fetal bovine serum - FBS (control); ii) normal FBS plus 1 M or 10 nM T3, for 12 h, and iii) FBS depleted of TH for 24 h (Tx). A decrease in proinsulin mRNA content and attachment to the cytoskeleton were observed in hypothyroid (Tx) beta cells. The amount of eEF1A protein anchored to the cytoskeleton was also reduced in hypothyroidism, and it is worth mentioning that ...
PJ Hale, I Jensen, RM Baddeley, M Nattrass; Insulin and Proinsulin Concentrations in Patients with Insulinoma before and after Surgical Treatment. Clin Sci (Lond) 1 January 1988; 75 (s19): 15P. doi: https://doi.org/10.1042/cs075015P. Download citation file:. ...
Inosine, guanosine and adenosine strongly stimulated proinsulin biosynthesis and insulin secretion in isolated mouse pancreatic islets. None of the purine ribonucleosides stimulated insulin secretion in rat islets, although as reported [jain & Logothetopoulos (1977) Endocrinilogy 100, 923-927] inosine and guanosine, but no adenosine, were potent stimulants of proinsulin biosynthesis in this species. The purine bases had no effect in either species. D-Ribose, which enhanced proinsulin biosynthesis at 0.3 and 0.6 mM but not at 5mM in rat pancreatic islets [jain & Logothetopoulos (1977) Endocrinology 100, 923-927], produced no secretory signals in rat islets and was without any effect on proinsulin biosynthesis and insulin secretion in mouse islets. The rates of oxidation of 14C-labelled purine ribonucleosides and D-ribose in islets of the two species correlated well with their effectiveness as inducers of insulin secretion and proinsulin biosynthesis. Specific inhibitors of purine ribonucleoside ...
Proinsulin is converted into insulin by the action of two endoproteases. Type I (PC1/PC3) is thought to cleave between the B-chain and the connecting peptide (C-peptide) and type II (PC2) between the C-peptide and the A-chain. An acidic region immediately C-terminal to the point of cleavage at the B-chain/C-peptide junction is well conserved throughout evolution and has been suggested to be important for proinsulin conversion [Gross, Villa-Komaroff, Kahn, Weir and Halban (1989) J. Biol. Chem. 264, 21486-21490]. We have here compared the precise role of this region as a whole and just the first acidic residue C-terminal to the point of cleavage in processing of proinsulin by PC3. To this end, several mutations were introduced in this region of human proinsulin (native sequence, B-chain RREAEDL C-peptide): RRPAEDL (C1Pro mutant); RRLAEDL (C1Leu mutant); RRL (C1-C4del mutant); RRE (del-C1Glu mutant). Mutant and native cDNAs were stably transfected into AtT20 (pituitary corticotroph) cells, in which ...
Purified Recombinant Human Proinsulin protein from Creative Biomart. Recombinant Human Proinsulin protein can be used for research.
We appreciate the comments of Stefan et al. (1) in this issue of Diabetes Care regarding adiponectin in youth. We are excited to have received the opinion of investigators in internal medicine, since traditionally pediatric investigations seldom cross the boundaries to adult medicine. The changing face of childhood diabetes might be playing a role (2). We offer the following responses.. 1) Our study demonstrated associations and correlations between adiponectin and proinsulin and the proinsulin-to-insulin ratio. We never implied that a direct effect of adiponectin on insulin secretory function exists. However, as recommended by Stefan et al., we investigated the relationship between the proinsulin-to-insulin ratio and adiponectin after adjusting for insulin sensitivity per metabolically active fat-free mass. The partial correlation coefficient of adiponectin to the proinsulin-to-insulin ratio after controlling for insulin sensitivity was r = −0.24, two-tailed P = 0.12, and one-tailed P = 0.06. ...
Our results from the 1-week culture at various glucose concentrations revealed that increasing glucose concentrations lead to an increased proinsulin secretion to the culture medium. We believe that the increase in proinsulin secretion could be explained by a sustained state of cellular activation.. The half-time of conversion of newly synthesized proinsulin from the intracellular pool was determined using three time points. In all experiments, except those in which islets were treated with IL-1β, the T1/2 was found to be 40-50 min when 15 min after the start of radioactive labelling was set as time 0. This agrees well with previously published studies (Steiner et al. 1972, Rhodes & Halban 1987 Nagamatsu et al. 1987) indicating an intracellular T1/2 of proinsulin of about 60 min in freshly isolated islets. In the present study, this rate of conversion was maintained after culture in glucose concentrations in the range 5.6-28 mM, whereas a decreased rate was measured only in islets which had ...
We have provided data showing that newborn girls have higher insulin and proinsulin concentrations and total proinsulin-to-insulin ratios in cord blood than newborn boys despite weighing less at birth. As insulin is a principal growth factor in utero, the higher insulin coupled with reduced growth in newborn girls suggests that girls are more insulin resistant in utero and after birth.. The higher insulin and proinsulin(s) in girls compared with boys for glucose/weight indicate insulin resistance in girls. The higher proinsulins in girls compared with boys have been noted before in neonates (11-13), and these are the more stable molecules. Changes in ratios and percentages may not have been seen if stability of insulin had not been maximized and, hence, was variable.. Our finding that insulin and insulin propeptides in cord blood are higher in girls than in boys is consistent with an intrinsic difference between the sexes, which is unlikely to be determined by environmental factors. Other ...
TY - JOUR. T1 - Dilation of the endoplasmic reticulum in beta cells due to molecular overcrowding?. Kinetic simulations of extension limits and consequences on proinsulin synthesis. AU - Despa, F.. PY - 2009/3. Y1 - 2009/3. N2 - Insulin regulates the energy homeostasis of the human body. This is synthesized in the endoplasmic reticulum (ER) of pancreatic beta cells from proinsulin. Chronic hyperglycemia increases considerably the proinsulin secretion, overcrowding the ER. Recent experimental evidence demonstrates that such states favor the proinsulin denaturation. The biophysical mechanism of this cellular dysfunction remains largely unknown. We use basic molecular principles and numerical simulations of time-dependent crowding conditions in the ER to show that crowding effects enhance the propensity of proinsulin molecules to (mis)fold in compressed, nonnative structures. Present results suggest: i) misfolding events and toxic accumulations increase dramatically if the proinsulin load exceeds ...
In the current study, the immunosenescence-like changes of T cells along with the progression of T1DM were found. This was associated with the expansion of some T-cell clones, at least partially the same between Tregs and Tconvs. Proinsulin-specific Tregs, mainly to proinsulin epitope 73-90, were mostly associated with counteracting immunosenescence-like changes and relieved immune response in the disease. Interestingly, clinical preparations of polyclonal Tregs contained preferentially expanded proinsulin-specific Tregs. Patients treated with adoptive transfer of these preparations were characterized by higher diversity of vβ TCR repertoire and a higher level of recent emigrants within proinsulin-specific Tregs.. Not surprisingly, like in the majority of chronic diseases, the T-cell compartment in T1DM underwent immunosenescence-like changes.17 When newly diagnosed (NDT1DM) patients were compared with long duration (LDT1DM) ones, it could be found a shift from naïve towards more ...
C57BL/KsJ db/db mice develop hyperphagic obesity and nonketotic diabetes similar to non-insulin-dependent diabetes mellitus in humans. Initially the mice demonstrate an abundant β-cell mass and hyperinsulinemia, which is followed by apparent β-cell loss. As an index of insulin synthesis, this study assesses pancreatic proinsulin mRNA, measured by dot hybridization to cloned cDNA, during the development of diabetes in the mice. Changes in proinsulin mRNA from 5 to 13 wk of age are compared with serum insulin, pancreatic insulin content, and blood glucose. In control (+ /db) mice, total proinsulin mRNA and pancreatic insulin content increased with age. Both changes were proportional to an increase in body weight. Obesity, hyperglycemia, and hyperinsulinemia were evident in diabetic (db/db) mice at 5 wk of age. Although pancreatic insulin content was comparable to that in the + /db controls at 5 wk, a fourfold relative elevation of proinsulin mRNA was observed. Despite an increase in body weight, ...
We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but ...
OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS - Nine SNPs at eight loci were associated with proinsulin levels (P , 5 × 10 -8 ). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four ...
It has been postulated that a glucose transporter of beta cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, we subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated beta-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia (glucose at 29 +/- 5 mg/dl), GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days (blood glucose at 57 +/- 7 mg/dl vs. 120 +/- 10 mg/dl in saline-infused control rats), GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively (P = 0.001). After 12 days (glucose at 54 +/- 8 mg/dl), GLUT-2 mRNA signal density was undetectable whereas proinsulin mRNA was reduced by 51%. After 12 days of hypoglycemia, the Km for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a ...
TY - JOUR. T1 - Disproportionate hyperproinsulinemia, Β-cell restricted prohormone convertase 2 deficiency, and cell cycle inhibitors Expression by human islets transplanted into athymic nude mice. T2 - Insights into nonimmune-mediated mechanisms of delayed islet graft failure. AU - Davalli, Alberto M.. AU - Perego, Lucia. AU - Bertuzzi, Federico. AU - Finzi, Giovanna. AU - La Rosa, Stefano. AU - Blau, Adam. AU - Placidi, Claudia. AU - Nano, Rita. AU - Gregorini, Luisa. AU - Perego, Carla. AU - Capella, Carlo. AU - Folli, Franco. PY - 2008/12/1. Y1 - 2008/12/1. N2 - To leam more about nonimmune-mediated islet graft failure, we transplanted different preparations (preps) of isolated human islets under the kidney capsule of streptozotocin (STZ)-diabetic nude mice. One month after the implantation of 1,000 or 2,000 islets, grafts were harvested for morphological, immunohistochemi-cal, and ultrastructural analysis. Only a single islet prep cured the diabetes out of all the recipients, while the ...
HYPERPROINSULINEMIA description, symptoms and related genes. Get the complete information in our medical search engine for phenotype-genotype relation
A frail 79-year-old lady with dementia presented with a 2-year history of frequent falls. Recurrent hypoglycaemic episodes were diagnosed and treated with continuous glucose infusion in multiple hospital admissions. Hypoadrenalism and hypothyroidism were ruled out. Whilst hypoglycaemic (blood glucose 1.6 mmol/L), both plasma C-peptide and proinsulin concentrations, were inappropriately elevated at 4210 pmol/L (174-960) and ,200 pmol/L (0-7) respectively with plasma insulin suppressed at 12 pmol/L (0-180). Whilst reported cases of proinsulinoma are typically pancreatic in origin, radiological investigations of the pancreas in this patient did not identify abnormalities. Unexpectedly contrast CT identified a heterogeneously enhancing mass (6.6 cm) at the lower pole of the left kidney consistent with renal cell carcinoma. Non-islet cell tumour-induced hypoglycaemia has been associated with renal malignancy; however, a serum IGF2:IGF1 ratio measured at ,10 effectively excludes this diagnosis. ...
To assess whether the discrepancy between the protein and mRNA levels was due to the presence of variant embryonic proinsulin transcripts, we carried out a detailed RT-PCR study during gastrulation, neurulation and early organogenesis (Fig 2). PCR with the P3 and P5 primers showed two amplification products (Fig 2A,B). Cloning and sequencing of these PCR products showed that the larger band corresponded to an alternatively spliced isoform (Pro1B1) of the embryonic proinsulin transcript; it retained intron 1 (717 nt) in the 5′ UTR, but spliced out intron 2 (3,432 nt). Both spliced and intron‐retained embryonic transcripts were polyadenylated, since oligo‐dT was used in the RT reaction. The intron 1 splicing pattern is developmentally regulated; the intron 1‐containing isoform was nearly undetectable during gastrulation (st. 4), and the percentage of intron 1 retention increased throughout neurulation (st. 8-10) and organogenesis (st. 12; Fig 2B,C). No PCR products were detected in the ...
Permanent neonatal diabetes mellitus (PNDM) is a rare disorder usually presenting within 6 months of birth. Although several genes have been linked to this disorder, in almost half the cases documented in Italy, the genetic cause remains unknown. Because the Akita mouse bearing a mutation in the Ins2 gene exhibits PNDM associated with pancreatic β cell apoptosis, we sequenced the human insulin gene in PNDM subjects with unidentified mutations. We discovered 7 heterozygous mutations in 10 unrelated probands. In 8 of these patients, insulin secretion was detectable at diabetes onset, but rapidly declined over time. When these mutant proinsulins were expressed in HEK293 cells, we observed defects in insulin protein folding and secretion. In these experiments, expression of the mutant proinsulins was also associated with increased Grp78 protein expression and XBP1 mRNA splicing, 2 markers of endoplasmic reticulum stress, and with increased apoptosis. Similarly transfected INS-1E insulinoma cells ...
INS_HUMAN] Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:176730].[1] [2] [3] [4] Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:125852]. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.[5] Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:606176]. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.[6] [7] Defects in INS are a cause of maturity-onset ...
TY - JOUR. T1 - The somatotropic axis in short children born small for gestational age. T2 - Relation to insulin resistance. AU - Woods, K. A.. AU - Van Helvoirt, M.. AU - Ong, K. K.L.. AU - Mohn, A.. AU - Levy, J.. AU - De Zegher, F.. AU - Dunger, D. B.. PY - 2002/1/1. Y1 - 2002/1/1. N2 - To determine whether hyperinsulinemia and reduced insulin sensitivity in individuals born small for gestational age (SGA) could be related to persisting abnormalities of the GH/IGF-I axis, we assessed overnight GH secretory profiles and measured fasting glucose, insulin, intact and 32,33 split proinsulin, and IGF-I levels in 16 short SGA children (age range 2.3-8.0 y) and in controls. Insulin sensitivity was calculated using the homeostasis model. Compared with short normal-birthweight controls (n = 7, age range 2.3-5.0 y), short SGA children had higher fasting insulin levels (means: 26.8 vs 20.6 pmol/L, p = 0.02), lower insulin sensitivity [means: 204 vs 284 %homeostasis model assessment (HOMA), p = 0.011, ...
ANN ARBOR, Mich. - University of Michigan scientists have identified events inside insulin-producing pancreatic cells that set the stage for a neonatal form of non-autoimmune type 1 diabetes, and may play a role in type 2 diabetes as well. The results point to a potential target for drugs to protect normally functioning proteins essential for producing insulin.. A study published online in the journal PLoS One shows that certain insulin gene mutations involved in neonatal diabetes cause a portion of the proinsulin proteins in the pancreas beta cells to misfold. Proinsulin proteins are the precursors of insulin, which the body needs to regulate blood sugar levels. Crucially, the misfolded mutant proteins cause normal proinsulin proteins in beta cells to misfold as well, the scientists found in studies of mouse and rat beta cells. Once the good proinsulin turns bad, it cannot be made into insulin and so the beta cells, and then the whole animal, become insulin deficient. The insulin ...
The ratio between proinsulin and insulin levels by IDA increased from in non-diabetics to in type II diabetics, whereas the ratio between C-peptide and insulin levels by IDA decreased.
Ultrapure peptides for research and drug discovery. Supplying prosinsulin, amyloids, toxins, insulins, knottins, proteins. Rapid therapeutic SAR
Mouse Monoclonal Anti-Insulin/Proinsulin Antibody (D3E7). Validated: EIA, IHC. Tested Reactivity: Human, Rat, Porcine, and more. 100% Guaranteed.
Australia, conclude that the protective effect is specific for islet pathology. The researchers explain that insulin and proinsulin could key autoantigens in ...
Je recherche des informations sur la nature des deux gènes de linsuline chez le rat pour étoffer létude dun document extrait de CELL vol 18 545-558, octobre 1979 : THE STRUCTURE AND EVOLUTION OF THE TWO NONALLELIC RAT PREPROINSULIN GENES. Le texte étant ancien je recherche quelles seraient les techniques utilisées pour résoudre une même problématique 20 ans après. Je vous remercie davance pour vos réponses. Caroline SANDRE -- Caroline SANDRE email: p6lbp269 at cicrp.jussieu.fr WWW : http://www.cicrp.jussieu.fr http://www.cicrp.jussieu.fr/p6lbp269 ...
The pathway is something like this : Pre proinsulin produced in Rough Endoplasmic Reticulum of Pancreas --, Transported to the Golgi apparatus and cleaved to form Proinsulin --, Packed into secretory granules --, In these granules proinsulin is converted to : Insulin and C peptide. - Traditionally it is said to have no intrinsic activity but recent studies say it might have anti oxidant and anti inflammatory properties. 2. What does it indicate ? ...
Affiliation:自治医科大学,医学部,助手, Research Field:内分泌・代謝学, Keywords:膵B細胞機能,プロインスリン分泌,プロインスリン,インスリン非依存性糖尿病,Proinsulin Secretion,糖負荷試験境界型,糖負荷試験 境昇型,糖尿病発症因子,肥満,Borderline Glucose Intolerance (IGT), # of Research Projects:1, # of Research Products:0
Jan wrote about the lumps and bumps from old Insulin To a large extent with genetically engineered insulin we dont get those lumps anymore. Many of those problems were caused by the proInsulin and c-peptide present in the animal origin insulins. rDNA insulin has no ProInsulin and no significant c-peptide. And it doesnt itch like the old pork-beef ones did and make those big hives. Of course there is a whole culture of DMers that want the insulin of yesteryear brought back, including my Texas cousin who says it works better, shes the same one who is afraid of Humulog. ---------------------------------------------------------- for HELP or to subscribe/unsubscribe, contact: [email protected] send a DONATION http://www.Insulin-Pumpers.org/donate.shtml ...
4. Describe the metabolic effects of insulin and the major ... 2. Understand the physiology of circulating insulin, C-peptide and proinsulin. ... - A free PowerPoint PPT presentation (displayed as a Flash slide show) on PowerShow.com - id: 559c9-ODZkY
expression of TCF7L2 alternative exons represents a tissue-specific signature; a unique splicing form of TCF7L2 is expressed in pancreatic islets, pancreas and colon but not in other tissues examined here; expression of this splicing form correlates with expression of proinsulin in glucose-stimulated pancreatic islets; expression of alternatively spliced forms of TCF7L2 in eight human tissues examined here is not associated with T2D-associated risk variants (PMID: 19602480 ...
Pham, M N; Kolb, H; Battelino, T; Ludvigsson, J; Pozzilli, P; Zivehe, F; Roden, M; Mandrup-Poulsen, T; Schloot, N C (2013). Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes. Diabetologia, 56(6):1356-1363.. Kaas, A; Pfleger, C; Hansen, L; Buschard, K; Schloot, N C; Roep, B O; Mortensen, H B; Schoenle, E J (2010). Association of adiponectin, interleukin (IL)-1ra, inducible protein 10, IL-6 and number of islet autoantibodies with progression patterns of type 1 diabetes the first year after diagnosis. Clinical and Experimental Immunology, 161(3):444-452.. Burkart, V; Siegenthaler, R K; Blasius, E; Vandenbroeck, K; Alloza, I; Fingberg, W; Schloot, N C; Christen, P; Kolb, H (2010). High affinity binding of hydrophobic and autoantigenic regions of proinsulin to the 70 kDa chaperone DnaK. BMC ...
Proinsulin antibody [C-PEP-01] (insulin) for ELISA, ICC/IF, IHC-P, RIA. Anti-Proinsulin mAb (GTX27761) is tested in Human samples. 100% Ab-Assurance.
TY - JOUR. T1 - Differential expression of rat pancreatic islet Beta-cell glucose transporter (GLUT 2), proinsulin and islet amyloid polypeptide genes after prolonged fasting, insulin-induced hypoglycaemia and dexamethasone treatment. AU - Koranyi, L.. AU - Bourey, R.. AU - Turk, J.. AU - Mueckler, M.. AU - Permutt, M. A.. PY - 1992/12/1. Y1 - 1992/12/1. N2 - The question posed by these studies was whether chronic adaptive changes in glucose-stimulated insulin secretion are accompanied by comparable changes in islet Betacell glucose transporter (GLUT 2) gene expression. Control, fasted (3-day), insulin-injected hypoglycaemic (5-day), and dexamethasone-treated (4-day) rats (n=5 for each condition), were studied. After fasting significant decrements in proinsulin mRNA/μg RNA (-32 %, p,0.05) and islet amyloid polypeptide mRNA/μg RNA (-44%, p,0.05) were observed, while there was no change in GLUT 2 mRNA/μg RNA (-13%, p,0.05). After insulin-induced hypoglycaemia, decrements in proinsulin mRNA/μg ...
The information in this video has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this video, especially if you are pregnant, nursing, taking medication, or have a medical condition.. ...
Insulin is a kind of peptide hormone which is critical for glucose homeostasis. The mature Insulin peptide is derived from Proinsulin, which includes the Insulin A and B chains connected by a peptide fragment (C-peptide). Proinsulin is processed within the endoplasmic reticulum of pancreatic beta cells into equimolar ratios of mature Insulin and C-peptide. Mouse C-peptide 1 is a single chain peptide composed of 29 amino acids, while C-peptide 2 is composed of 31 residues. C-peptide is secreted together with insulin.. The role of C-peptide has been considered to keep the best configuration to form three disulfide bonds, and has no biological activity, however, recent studies indicated that C-peptide can bind, probably, a G-protein coupling specific receptor present on the surface of endothelial cells, kidney microtubule cells and fibroblasts, resulting in activation of calcium-dependent intracellular signaling, activation of Na+-K+-ATPase, and enhancement of NO synthesis. Administration of ...
United States: P. Gottlieb, Denver, CO; J. Skyler, Miami, FL; R. Hays, Wellington, FL; F. Ovalle, Birmingham, AL; V. Aroda/R. Ratner, Washington, DC; J. Berg/M. Kipnes, San Antonio, TX; L. Zemel, Denver, CO; M. Rendell, Omaha, NE; P. Norwood, Fresno, CA; P. Raskin, Dallas, TX. Australia/New Zealand: P. Colman, Melbourne; M. Gerstman, Victoria; T. Davis, Fremantle; V. Heazlewood, Queensland; J. Baker, Auckland; P. Dunn, Hamilton; R. Scott, Christchurch; J. Krebs, Wellington. ClinicalTrials.gov registration number: NCT00453375. ...
Tight glycemic control is mandatory for the prevention and treatment of vascular complications in patients suffering from diabetes mellitus. After onset of Type 2 Diabetes, patients are usually treated with diet along with or without different combinations of oral drugs. One first-line drug class are sulfonylurea drugs that are preferably provided to patients who are not obese. The mode of action of sulfonylurea drugs is to increase beta-cell secretion, but it could be shown that they lead to deterioration of the beta-cell secretion product over time, resulting in increased proinsulin secretion. Since proinsulin is an independent cardiovascular risk factor, recent publications have demonstrated an increased risk for cardiovascular events in patients treated with sulfonylurea drugs as compared to other treatment methods.. Combination therapy of sulfonylurea drugs with glitazones has been shown to counterbalance the effect of deteriorated beta-cell secretion and to improve insulin sensitivity and ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
The cookie settings on this website are set to allow cookies to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click Accept below then you are consenting to this.. Close ...
The information in this video has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this video, especially if you are pregnant, nursing, taking medication, or have a medical condition.. ...
To our knowledge, our study is the first to comprehensively assess islet cell responsivity in people with T1D using gold-standard methods across the spectrum of detectable C-peptide production. The group with high peak C-peptide (,0.400 pmol/mL) during an MMTT exhibited lower fasting glucose (111 ± 31 mg/dL), hemoglobin A1c (6.8% ± 1.0%), and mean glucose (140 ± 25 mg/dL), and greater CGM-derived time in target range (72% ± 12%). Given that the high C-peptide group was considerably less often hyperglycemic based on CGM, the lack of difference in peripheral or hepatic insulin sensitivity across the groups supports that insulin resistance in T1D is not strongly related to hyperglycemia as suggested by others (26). The high C-peptide group was the only group who demonstrated β cell responsivity to glucose during the hyperglycemic clamp conducted during the GPA test, with measurable increases in C-peptide and proinsulin secretion. Furthermore, this group also demonstrated α cell responsivity ...
The pancreotoxicity of cyproheptadine (CPH) in rats was characterized through measurement of proinsulin and insulin levels in the pancreas as well as plasma immunoreactive insulin (IRI) and glucose levels at various times during and after drug treatment. Daily oral doses of CPH (45 mg/kg) depleted pancreatic IRI to 25% of control within 3 days. Pancreatic IRI levels showed no further decrease during the rest of a 2-week treatment period and returned to normal levels 2 days after withdrawal of the drug. Pancreatic proinsulin levels were not significantly changed by CPH treatment, and the decrease in pancreatic IRI can be ascribed primarily to a decrease in insulin. Nonfasting hyperglycemia was evident after two doses of CPH and persisted throughout the treatment period. Plasma IRI was not significantly altered compared to control and was inappropriately low for the hyperglycemia that was produced by CPH. Daily doses of CPH given i.p. (45 mg/kg) caused a transient decrease in pancreatic IRI, but ...
Susan, There a couple of answers; First, many people are more insulin resistant in the morning (part of the dawn phenomenon). This would explain your need for more insulin during the AM, both for meals and for your basal rate. Second, many people (Im told) have different insulin to carb during different times of the day. I would say that if you raise your AM basal to the point where your meal ratio is equal to the other times of the day, you will crash if you skip or delay breakfast. Just some observations that I have made. Good luck. Mario ----- Original Message ----- From: Susan Russell ,email @ redacted, To: ,email @ redacted, Sent: Tuesday, December 05, 2000 11:41 AM Subject: [IP] re: Carb to Insulin Ratio Fluctuations , For you medical buffs I need some clarification here. I am a sufferer of , varying CHO to insulin ratios throughout the day. i.e.: , , 1. Breakfast = 5 to 8 gms of CHO to 1 unit of insulin (big differences here) , (eat same toast+8 gms protein+coffee/cream almost daily) , ...
Inside the pancreas, the hormone insulin is made in the beta cells, which are part of the Islets of Langerhans. These islets also have alpha cells, which make glucagon, as well as delta cells. With each meal, beta cells release insulin to help the body use or store the blood sugar it gets from food.. In the beta cells, insulin is created first as a big molecule called proinsulin. Proinsulin is broken into two pieces: insulin and C-peptide. C-peptide is important especially when determining treatment because it can be used to measure how much insulin a person is making. The more C-peptide a person has, the more insulin they are making. This can help a provider determine how much insulin to prescribe. In people with type 1 diabetes, the pancreas no longer makes insulin. The beta cells have been destroyed and they need insulin shots to use glucose from meals.. People with type 2 diabetes make insulin, but their bodies dont respond well to it. Some people with type 2 diabetes need diabetes pills ...
Additional file 1: Table S1. of The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors
Insulin testing may be used to help diagnose an insulinoma, and diagnose the cause of hypoglycemia in an individual with signs and symptoms Identify insulin resistance - Monitor the amount of insulin produced by the beta cells in the pancreas (endogenous); in this case, a C-peptide test may also be done. Insulin and C-peptide are produced by the body at the same rate as part of the conversion of proinsulin to insulin in the pancreas. - Determine when a type 2 diabetic might need to start taking insulin to supplement oral medications - Determine and monitor the success of an islet cell transplant intended to restore the ability to make insulin, by measuring the insulin-producing capacity.Insulin is produced by beta cells of the pancreas. It leads to Type 1 diabetes caused by Insulin deficiency & Type 2 diabetes caused by insulin resistance. This assay is useful in the management of Diabetes. It is also used for diagnosing Insulinoma when used in conjunction with Proinsulin and C-peptide ...
Importance: Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
To review, in my last post, discussing this paper, a seminal observation/conclusion can be summed up as follows: Insulin is formed in stepwise fashion from a larger protein (preproinsulin) that has a terminal signaling chain cleaved forming proinsulin that is then folded, cross-linked and has one of the three main chains cleaved in the last step(s) resulting in a protein with two parallel chains, insulin. I like this newer representation I found below because it provides the numbers in the amino acid sequence at which the cuts are made. This is important to better understanding the papers Im going to discuss here ...
GAD2 maps to chromosome 10p11.23 and encodes the 65-kDa isoform of GAD65, a major autoantigen in type 1 diabetes. The genetic variation that influences expression of preproinsulin mRNA, encoding another major autoantigen in type 1 diabetes, has already been shown to be genetically associated with disease. Previous reports that have assessed the association of GAD2 with type 1 diabetes have not used a dense map of markers surrounding the gene and have relied on very small clinical sample sizes. Consequently, no definite conclusions can be drawn from their negative results. We have therefore systematically searched all exons, the 3 untranslated region (UTR), the 5 UTR, and the 5 upstream region of GAD2, for polymorphisms in 32 white European individuals. We have genotyped these polymorphisms in a maximum of 472 U.K. type 1 diabetic affected sib pair families exhibiting linkage to type 1 diabetes on chromosome 10p and have tested both single variants and haplotypes in the GAD2 region for association
Diagnosis is based on anamnesis, examination results (including neurological examination) and registered a decline of plasma glucose in those cases where it is proved that the secretion of insulin with enhanced or not inhibitedand excluded other causes of hypoglycemia (use of hypoglycemic agents, diseases of the hypothalamic-pituitary system, adrenal lesions, hepatic failure, some other tumors).. To do this, carry out a test with fasting, investigate the secretion of proinsulin, C-peptide, cortisol.For the differential diagnosis and clarify the features may require instrumental examination (ultrasound, CT angiography).. Treatment is aimed at the normalization of plasma glucose levels.Possible subsequent surgery to remove the tumor.Patients with metastatic or ineffective surgical treatment is prescribed chemotherapy.. ...
C-Peptide, Human, 10 mg. The measurement of the C-peptide under standardized conditions provides a sensitive well accepted and clinically validated assessment of ��-cell function.
"A bacterial clone synthesizing proinsulin". Proc Natl Acad Sci U S A. 75: 3727-31. doi:10.1073/pnas.75.8.3727. PMC 392859 . ... the first author of the landmark report from the Gilbert laboratory showing that bacteria could be induced to make proinsulin- ...
"A bacterial clone synthesizing proinsulin". Proceedings of the National Academy of Sciences of the United States of America. 75 ...
The signal sequence is cleaved from the N-terminus of the peptide by a signal peptidase, leaving proinsulin. After proinsulin ... Proinsulin C-peptide was first described in 1967 in connection with the discovery of the insulin biosynthesis pathway. It ... Nordquist L, Brown R, Fasching A, Persson P, Palm F (November 2009). "Proinsulin C-peptide reduces diabetes-induced glomerular ... Clark PM (1999). "Assays for insulin, proinsulin and C-peptide". Ann Clin Biochem. 36: 541-564. Shapiro ET, Tillil H, ...
The endoproteases PC1/3 and PC2 aid in this transformation from proinsulin to insulin; and (3) the clathrin protein coat is ... proinsulin becomes insulin through the process of proteolysis. ...
It was noted that the proinsulin mRNA remained stable. This suggests that the acute response to glucose of the insulin ... The exposure of rat Langerhans islets to glucose for 1 hour is able to remarkably induce the intracellular proinsulin levels. ...
The name of the precursor for a protein is often prefixed by pro-. Examples include proinsulin and proopiomelanocortin, which ...
Proinsulin The substance made first in the pancreas that is then made into insulin. Proliferative retinopathy damage to the ... Purified insulins Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help ... While being stored in pancreatic beta cells, proinsulin includes both insulin and C-peptide, which is freed before insulin ...
"Evidence for an interaction between proinsulin C-peptide and GPR146". The Journal of Endocrinology. 218 (2): B1-8. doi:10.1530/ ...
Goodge KA, Hutton JC (August 2000). "Translational regulation of proinsulin biosynthesis and proinsulin conversion in the ...
The C-peptide is the central portion of proinsulin, and the primary sequence of proinsulin goes in the order "B-C-A" (the B and ... forming proinsulin. In the RER the proinsulin folds into the correct conformation and 3 disulfide bonds are formed. About 5-10 ... The C-peptide of proinsulin (discussed later), however, differs much more among species; it is also a hormone, but a secondary ... Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone ...
Defects in proinsulin conversion. *Insulin gene mutations. *Insulin receptor mutations. *Exocrine pancreatic defects *Chronic ...
Finally, proinsulin is converted into the bioactive hormone insulin by removal of the C-peptide. Almost no preproinsulin exists ... Preproinsulin is a proinsulin molecule with a signal peptide attached to its N-terminus. Preproinsulin is a biologically ... Preproinsulin is converted into proinsulin by signal peptidases, which remove its signal peptide from its N-terminus. ... and proinsulin, a stable ER intermediate. Proprotein convertase 1, proprotein convertase 2 preproinsulin definition in the ...
"Human Krüppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells". Diabetologia. 50 (7): 1433- ...
... proinsulin, and proinsulin-like material). The term is composed of hyper - high, proinsulin - immature insulin molecule, and - ... September 2003). "Disruption of a receptor-mediated mechanism for intracellular sorting of proinsulin in familial ...
... statins and C-peptide of proinsulin, Method(s) of stabilizing and potentiating the actions and administration of brain-derived ... statins and C-peptide of proinsulin". US Patent 20020077317. Justia Patents. Undurti Narasimha Das, Appa Rao Allam (September ... statins and C-peptide of proinsulin". US Patent 20020077317. Justia Patents. Undurti Narasimha Das (January 16, 2003). "Methods ...
Ko, A.S.C., Smyth, D.G., Markussen, J. and Sundby, F. (1971) The amino acid sequence of the C-peptide of Human Proinsulin. Eur. ... Massey, D.E. and Smyth, D.G. (1975) Guinea Pig Proinsulin: primary structure of the C-peptide isolated from pancreas. J. Biol. ... Salokangas, A., Smyth, D.G., Markussen,J. and Sundby, F. (1971) Bovine Proinsulin: amino acid sequence of the C-peptide ... Snell, C.R. and Smyth, D.G. (1975) Proinsulin: a proposed three dimensional structure. J. Biol. Chem., 250, 6291-6295. 26. ...
"Aggregation and lack of secretion of most newly synthesized proinsulin in non-beta-cell lines". Endocrinology. 145 (8): 3840-9 ...
Malaguarnera R, Sacco A, Voci C, Pandini G, Vigneri R, Belfiore A (May 2012). "Proinsulin binds with high affinity the insulin ...
The proinsulin is then cleaved at two positions to yield two polypeptide chains linked by two disulfide bonds. Removal of two C ... Insulin, for example, is synthesized as preproinsulin, which yields proinsulin after the signal peptide has been cleaved. ... Protein folding occurs in the single-chain Proinsulin form which facilitates formation of the ultimately inter-peptide ...
"The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin". J Biol Chem. 253 (8 ...
H.W. Davidson; C.J. Rhodes; J.C. Hutton (1988). "Intraorganellar calcium and pH control proinsulin cleavage in the pancreatic ...
... can also stimulate proinsulin folding as well, as it can serve as a molecular chaperone for insulin. In the diagnosis ...
... activity and chaperone function of human protein-disulfide isomerase are required for the efficient refolding of proinsulin". ...
... since proinsulin and proIAPP are cosecreted, this results in an increase in the production of proIAPP as well. Although little ... resistance in Type 2 diabetes produces a greater demand for insulin production which results in the secretion of proinsulin. ...
PCSK1 and PCSK2 differentially cleave proopiomelanocortin and they act together to process proinsulin and proglucagon in ...
... contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin. ... October 2011). "Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides ...
Study results from Eli Lilly and Company in the area of proinsulin published. , HighBeam Business: Arrive Prepared ( ...
More modification can occur in the secretory vesicles (for example insulin is cleaved from proinsulin in the secretory vesicles ...
... folding of proinsulin occurs forming three disulfide bonds.[5] Subsequent to protein folding, proinsulin is transported to the ... it simultaneously increases proinsulin biosynthesis, mainly through translational control.[3] ... the signal peptide is cleaved to form proinsulin.[5] Then, ... apparatus and enters immature insulin granules where proinsulin ...
Mouse Monoclonal Anti-Insulin/Proinsulin Antibody (D3E7). Validated: EIA, IHC. Tested Reactivity: Human, Rat, Porcine, and more ... Blogs on Insulin/Proinsulin. There are no specific blogs for Insulin/Proinsulin, but you can read our latest blog posts. ... PTMs for Insulin/Proinsulin Antibody (NB200-435). Learn more about PTMs related to Insulin/Proinsulin Antibody (NB200-435). ... Publications for Insulin/Proinsulin Antibody (NB200-435) (0). There are no publications for Insulin/Proinsulin Antibody (NB200- ...
Anti-Proinsulin mAb (GTX27761) is tested in Human samples. 100% Ab-Assurance. ... Proinsulin antibody [C-PEP-01] (insulin) for ELISA, ICC/IF, IHC-P, RIA. ... The antibody can be used for RIA and ELISA estimation of human proinsulin C-peptide or human proinsulin in body fluids. ... Storage Conditions: Proinsulin antibody [C-PEP-01]. Storage Buffer. Phosphate buffered saline pH 7.4 containing 15mM sodium ...
Insulin and Proinsulin Concentrations in Patients with Insulinoma before and after Surgical Treatment PJ Hale PJ Hale ... Proinsulin processing in the rat insulinoma cell line INS after overexpression of the endoproteases PC2 or PC3 by recombinant ... Identification of a chromogranin A-like precursor and its parallel processing with proinsulin Biochem J (June, 1987) ... PJ Hale, I Jensen, RM Baddeley, M Nattrass; Insulin and Proinsulin Concentrations in Patients with Insulinoma before and after ...
Metabolic signals produced by purine ribonucleosides stimulate proinsulin biosynthesis and insulin secretion. K Jain, J ... D-Ribose, which enhanced proinsulin biosynthesis at 0.3 and 0.6 mM but not at 5mM in rat pancreatic islets [jain & ... Inosine, guanosine and adenosine strongly stimulated proinsulin biosynthesis and insulin secretion in isolated mouse pancreatic ... Metabolic signals produced by purine ribonucleosides stimulate proinsulin biosynthesis and insulin secretion ...
Sequence requirements for proinsulin processing at the B-chain/C-peptide junction. J E Kaufmann, J C Irminger, P A Halban ... and kinetics of proinsulin conversion were studied (pulse-chase/HPLC analysis of proinsulin-related peptides). The results show ... Proinsulin is converted into insulin by the action of two endoproteases. Type I (PC1/PC3) is thought to cleave between the B- ... To this end, several mutations were introduced in this region of human proinsulin (native sequence, B-chain RREAEDL C-peptide ...
Therefore, the effects of TH on proinsulin gene expression are not known. This led us to measure: a) proinsulin mRNA expression ... Hypothyroidism decreases proinsulin gene expression and the attachment of its mRNA and eEF1A protein to the actin cytoskeleton ... Proinsulin poly(A) tail length and cytoskeleton arrangement remained unchanged in hypothyroidism. T3 treatment of control cells ... The data indicate that TH is important for proinsulin mRNA expression and translation, since its total amount and attachment to ...
... The expression of transgenic proinsulin II. prevents the onset of ... the thymus, to induce tolerance to proinsulin... in nonobese diabetic mice. Mice that expressed the transgenic proinsulin did ... Re: Autoimmunity To Proinsulin Pivotal In IDDM Development jyoti amin____ Tid:14:30, Datum:01/11/100 (. 0) SKICKA REPLIK PÅ D ... Autoimmunity To Proinsulin Pivotal In IDDM Development. [ Läs eventuella Repliker på detta inlägg ] [ Skicka Replik på detta ...
Recombinant Human Proinsulin protein can be used for research. ... Recombinant Human Proinsulin protein. INS Related Products By ... Purified Recombinant Human Proinsulin protein from Creative Biomart. ... Recombinant Human Proinsulin(Phe25 -Asn110) was expressed in E. coli. Description :. After removal of the precursor signal ... Home / Products / Recombinant Proteins / Recombinant Human Proinsulin protein ...
90-104-proinsulin. As compared with NDT1DM, the percentage of Tregs specific for 90-104-proinsulin was higher in LDT1DM (figure ... 73-90-proinsulin. The most informative was the response to proinsulin epitope 73-90. As compared with patients with NDT1DM, the ... 10-18-Β-chain-proinsulin (CD8+ T cells). The percentage of proinsulin-specific CD8+ T cells was higher in patients with LDT1DM ... Proinsulin-specific Tregs, mainly to proinsulin epitope 73-90, were mostly associated with counteracting immunosenescence-like ...
A raised proinsulin-to-insulin ratio (proinsulin/insulin) due to impaired processing of proinsulin is an early marker of beta ... Proinsulin levels and proinsulin/insulin increased across age groups in both genders. After adjustment, greater age was ... In regression analyses we assessed the relationships between age and insulin, proinsulin, and proinsulin/insulin, while ... together with positive associations of age with proinsulin and proinsulin/insulin, point towards a loss of beta cell function ...
The amount of proinsulin generated by Pro1B1 messenger RNA was 2.5‐fold lower than that generated by Pro1B mRNA. (B) Proinsulin ... Embryonic proinsulin protein and messenger RNA content. (A) Proinsulin was measured in extracts of pools of 18 embryos of stage ... Note that chick proinsulin protein levels might be underestimated as a rat insulin/proinsulin RIA kit was used. (B) ... Modulation of the proinsulin splicing pattern. (A) Diagram of embryonic regions. (B,C) Proinsulin reverse transcription-PCR (RT ...
The ratio between proinsulin and insulin levels by IDA increased from in non-diabetics to in type II diabetics, whereas the ... Proinsulin is normally converted to insulin and C-peptide in the beta cells. Hypersecretion of proinsulin by a tumor overwhelms ... Human insulin, as well as porcine and bovine insulin, proinsulin, and C-peptide, did not bind to this by: Proinsulin-to-C- ... Proinsulin-like components (proinsulin and its intermediate forms, PLC) and C-peptide have been identified as secretory ...
Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: The Insulin Resistance ... title = "Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: The Insulin ... Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: The Insulin Resistance ... Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes : The Insulin ...
Proinsulin content (ng/10 islets). PI/PI+I (%). Insulin and proinsulin content in rat pancreatic islets cultured at different ... High concentrations of proinsulin and abnormal proinsulin conversion have been associated with type II diabetes (T2D) as well ... During the culture period, the proinsulin accumulation in media from islets kept at 11 mM glucose was 0.5 ng proinsulin per 10 ... The endoproteolytic processing of proinsulin to insulin is mediated by proinsulin convertases 1 and 2 (PC1 and PC2) (Bailyes et ...
C-peptide and proinsulin. ... - A free PowerPoint PPT presentation (displayed as a Flash slide show) on PowerShow.com - id: ... Dalton precursor (pre-proinsulin) which is processed to final secreted products (proinsulin, insulin, C-peptide). ... Processing of Proinsulin to Insulin and C-peptide. Signal Peptide. Arg-Arg. Lys-Arg. Pre B Chain Connecting A Chain. Peptide. C ... Processing of Proinsulin to Insulin and C-peptide. Signal Peptide. Arg-Arg. Lys-Arg. Pre B Chain Connecting A Chain. Peptide. ...
In humans, proinsulin is encoded by the INS gene. The islets of Langerhans only secrete between 1% and 3% of proinsulin intact ... Proinsulin was discovered by Professor Donald F. Steiner of the University of Chicago in 1967. Proinsulin is made up of 81 ... Postnatal proinsulin is crucial for metabolic regulation. However, proinsulin in neonates is important for normal development ... Additionally, while proinsulin and insulin have structural differences, proinsulin does demonstrate some affinity for the ...
proinsulin;. DM,. diabetes mellitus;. SEAP,. secreted alkaline phosphatase.. *© 2007 by The National Academy of Sciences of the ... Proinsulin maturation, misfolding, and proteotoxicity. Ming Liu, Israel Hodish, Christopher J. Rhodes, and Peter Arvan ... As a tool to explore proinsulin (PI) trafficking, a human PI cDNA has been constructed with GFP fused within the C peptide. In ... Of these, a case can be made for proinsulin (PI) misfolding with resultant endoplasmic reticulum (ER) stress as a proximal ...
The idea is that if misfolded proinsulin is chopped up and degraded, then the remaining normal proinsulin can move through the ... We also found that in animals in which production of misfolded proinsulin molecules reaches 30 percent of total proinsulin, ... But, when the misfolded proinsulin physically attaches itself to the normal bystander proinsulin, that blocks the ability of ... researching-proinsulin-misfolding-to-understand-diabetes More in Medicine & Health. * Researchers at LSTM take a novel approach ...
Bos taurus proinsulin mRNA, partial cds Bos taurus proinsulin mRNA, partial cds. gi,397914146,gb,JX041514.1, ...
Wikipedia Proinsulin 2007 http://en.wikipedia.org/wiki/Proinsulin. *Davidson, H. Proinsulin processing. Cell Biochemistry and ... GM Safflower with Human Pro-Insulin. Regulators show cavalier disregard for the safety of threatened species as well as human ... line 4438-5A that produces human pro-insulin. The transgenic safflower was engineered to express an oleosin-human pro-insulin ... Pro-insulin is the precursor to insulin, normally made in the beta cell of the islets of Langerhans of the human pancreas. The ...
S. M. Hampton, K. Beyzavi, D. Teale, and V. Marks, "A direct assay for proinsulin in plasma and its applications in ... Hypoglycemic Syndrome in a Patient with Proinsulin-Only Secreting Pancreatic Adenoma (Proinsulinoma). Gian Paolo Fadini,1 ... A. Piovesan, A. Pia, G. Visconti et al., "Proinsulin-secreting neuroendocrine tumor of the pancreas," Journal of ... G. Clark, C. Sadur, and B. Puligandla, "Multiple proinsulin-secreting tumors of the pancreas treated by laparoscopic distal ...
C: Proinsulin mRNA. D: Proinsulin biosynthesis per islet. E: Specific proinsulin biosynthesis normalized to total protein ... glucose also increases proinsulin mRNA content by both stimulating proinsulin gene transcription and stabilizing proinsulin ... 1). Basal proinsulin mRNA decreased over time in culture; however, the stimulatory effect of glucose on proinsulin biosynthesis ... Proinsulin biosynthesis is expressed in dpm/islet (top), and specific proinsulin biosynthesis (bottom) is calculated as the ...
... proinsulin cysteine residues impose dominant-negative inhibition on wild-type proinsulin transport. PLoS ONE 5: e13333. ... Human proinsulin is not processed to insulin in developing eye cells, but can be induced to do so by overexpressing a secretory ... 2014 Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin. Genetics 196: 557-567 ... Genetic Complexity in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin. Soo-Young Park, Michael Z. Ludwig, ...
Role of prepancreatic (pro)insulin and the insulin receptor in prevention of embryonic apoptosis.. Morales AV1, Serna J, ... The characterization of (pro)insulin as an early embryonic growth factor requires demonstration of its expression and cellular ... To analyze the prepancreatic (pro)insulin effect on apoptotic cell death, we treated embryos with antisense ...
Increased β-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans. Teresa Mezza, Pietro M. Ferraro, Vinsin A. Sun, ... Increased β-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans. Teresa Mezza, Pietro M. Ferraro, Vinsin A. Sun, ... Increased β-Cell Workload Modulates Proinsulin-to-Insulin Ratio in Humans Message Subject (Your Name) has forwarded a page to ... Increased proinsulin secretion, which characterizes type 2 diabetes and insulin resistance, may be due to an intrinsic, ...
We previously demonstrated that human proinsulin C-peptide can protect against vasculopathy in diabetes; however, its role in ... Proinsulin C-peptide prevents impaired wound healing by activating angiogenesis in diabetes J Invest Dermatol. 2015 Jan;135(1): ... We previously demonstrated that human proinsulin C-peptide can protect against vasculopathy in diabetes; however, its role in ...
Native proinsulin (PI) belongs to the class of the difficult-to-express proteins in Escherichia coli. Problems mainly arise due ... A radioligand-binding assay for detecting antibodies specific for proinsulin and insulin using 35S-proinsulin. J Immunol ... Mackin RB (1998) Proinsulin: recent observations and controversies. Cell Mol Life Sci 54(7):696-702CrossRefGoogle Scholar ... Native proinsulin (PI) belongs to the class of the difficult-to-express proteins in Escherichia coli. Problems mainly arise due ...
... about PROINSULIN. Search and download thousands of Swedish university dissertations. Full text. Free. ... Search for dissertations about: proinsulin. Showing result 1 - 5 of 44 swedish dissertations containing the word proinsulin. ... Keywords : MEDICIN OCH HÄLSOVETENSKAP; MEDICAL AND HEALTH SCIENCES; Proinsulin; insulin; glucose; obesity; bariatric surgery; ... Keywords : haemostatis; lipoprotein a ; MTHFR; homocysteine; proinsulin; leptin; apolipoprotein A1; DHEAS; myocardial ...
The IAA in serum will link the Sulfo-tagged proinsulin to the biotinylated proinsulin, which will be captured on the solid ... Proinsulin/Insulin Autoantibodies Measured With Electrochemiluminescent Assay Are the Earliest Indicator of Prediabetic Islet ... The ECL-IAA using Meso Scale instrumentation and ruthenium-labeled proinsulin is a nonradioactive IAA assay in which bivalent ... Proinsulin/Insulin Autoantibodies Measured With Electrochemiluminescent Assay Are the Earliest Indicator of Prediabetic Islet ...
Antilipolytic effect of proinsulin C-peptide in diabetic rat. International Conference and Exhibition on Metabolomics & Systems ...
Here, we demonstrate that a novel combination treatment with anti-CD3ε-specific antibody and i.n. proinsulin peptide can ... Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. ... Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs. ...
Anti-Proinsulin mAb (GTX28300) is tested in Human samples. 100% Ab-Assurance. ... Proinsulin, P01308, 3630, 125850, INS. Specificity. Kd for this antibody is >3 x 10-8MDoes not cross-react with human, bovine ... removal of proinsulin molecules from serum samples before the measurement of insulinic C-peptide. ... of a sensitive two-site sandwich enzyme-linked/RIA immunosorbent assays for the measurement of intact human proinsulin in serum ...
T cells specific for proinsulin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce ... Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP J Clin Invest. 2006 Dec;116( ... As cytotoxic T cells specific for IGRP were not detected in transgenic NOD mice tolerant to proinsulin, we determined that ... Our results suggest that pathogenic proinsulin-specific immunity in NOD mice subsequently spreads to other antigens such as ...
You are here: Home Products by Molecule of Interest Proinsulin Proinsulin. Proinsulin (PI), a polypeptide of 9390 MW (86 amino ... The measurement of Proinsulin in serum provides useful valuable information for the diagnosis of insulinomas. Proinsulin levels ... The sequence of proinsulin is highly conserved in mammalian species and is homologous with IGF-1 and IGF-2. This protein is ... In normal individuals, proinsulin is present in the circulatioon in very low concentrations (typical basal values 2-6 pmol/l). ...
Effects of monensin on biosynthesis and intracellular processing of proinsulin J. E. Smith; J. E. Smith ... J. E. Smith, M. Tyhurst, S. L. Howell; Effects of monensin on biosynthesis and intracellular processing of proinsulin. Biosci ... Monensin, a specific sodium ionophore, has been shown to reduce glucose-induced proinsulin biosynthesis by 30% and to ... Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65-66 split and 32-33 split proinsulins ...
Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin ... Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from ... Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.. [Laura Fernández-Sánchez ... These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa. ...
Discover a faster, simpler path to publishing in a high-quality journal. PLOS ONE promises fair, rigorous peer review, broad scope, and wide readership - a perfect fit for your research every time. Learn More Submit Now ...
Chemiluminescent Human Total Proinsulin ELISA measures all forms of proinsulin in serum, plasma, and tissue culture with a ... The STELLUX® Chemi Human Total Proinsulin ELISA offers superior sensitivity compared to other kits in the market. The assay ... measures intact as well as Des (31,32) and Des (64,65) proinsulin. ...
Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 ... Figure 3 Processing of proinsulin by lysosomal proteases. A) Proinsulin was incubated with selected cathepsins in vitro for 2 h ... Proinsulin is one of the major target autoantigens in T1D [1]. Consequently, processing and presentation of proinsulin exhibit ... The processing of proinsulin and identification of proinsulin-derived T cell epitopes can provide key elements of the disease ...
A high quality ELISA for human proinsulin in serum or plasma. Highly specific with no cross-reactivity to human insulin or C- ... msds for Mercodia Proinsulin ELISA. Proinsulin ELISA MSDS EN. Proinsulin ELISA MSDS DK. Proinsulin ELISA MSDS FR. Proinsulin ... Proinsulin ELISA MSDS IT. Proinsulin ELISA MSDS NO. Proinsulin ELISA MSDS PT. Proinsulin ELISA MSDS ES. Proinsulin ELISA MSDS ... Rat/Mouse Proinsulin ELISA MSDS EN. Rat/Mouse Proinsulin ELISA MSDS DK. Rat/Mouse Proinsulin ELISA MSDS FR. Rat/Mouse ...
  • Chronic hyperglycemia increases considerably the proinsulin secretion, overcrowding the ER. (elsevier.com)
  • Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. (mendelian.co)
  • In order to elucidate a possible relationship between β-cell function and conversion of proinsulin to insulin, isolated rat pancreatic islets were maintained in tissue culture for 1 week at various glucose concentrations (5.6-56 mM). (bioscientifica.com)
  • Biosynthesis of proinsulin in β-cells is stimulated by glucose and this imposes an increased demand on the mechanism for proinsulin to insulin conversion. (bioscientifica.com)
  • The objective of this paper was to compare fasting intact and split proinsulin-to-insulin ratios (PI/I, SPI/I) with intact and split proinsulin-to-C-peptide ratios (PI/C-pep, SPI/C-pep) in the prediction of type 2 diabetes. (uthscsa.edu)
  • Insulin sensitivity (S I ) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests, and fasting intact and split proinsulin were measured using specific two-site monoclonal antibody-based immunoradiometric assays. (uthscsa.edu)
  • To determine whether hyperinsulinemia and reduced insulin sensitivity in individuals born small for gestational age (SGA) could be related to persisting abnormalities of the GH/IGF-I axis, we assessed overnight GH secretory profiles and measured fasting glucose, insulin, intact and 32,33 split proinsulin, and IGF-I levels in 16 short SGA children (age range 2.3-8.0 y) and in controls. (elsevier.com)
  • Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. (mendelian.co)
  • ELISA measurements revealed that culture at increased glucose concentrations as well as islet exposure to IL-1β increased proinsulin accumulation in the culture media. (bioscientifica.com)
  • RESEARCH DESIGN AND METHODS - We have conducted a meta-analysis of genome-wide association tests of ;2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. (emory.edu)
  • There are currently no images for Insulin/Proinsulin Antibody (NB200-435). (novusbio.com)
  • FAQs for Insulin/Proinsulin Antibody (NB200-435). (novusbio.com)
  • In the pancreas, within specialized cells called beta cells, proinsulin, a biologically inactive molecule, is split apart to form one molecule of C-peptide and one. (dr-peshev.com)
  • Insulin ( INS ) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. (mendelian.co)
  • Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. (mendelian.co)
  • Hypersecretion of proinsulin by a tumor overwhelms this proteolytic pathway, resulting in the release of proinsulin into the circulation. (dr-peshev.com)
  • Our hypothesis was that in a general population, signs of deterioration of beta cell function with advancing age is indicated not only by a decrease in random insulin levels, but also by a corresponding increase in proinsulin and proinsulin/insulin. (biomedcentral.com)
  • We hypothesised that in a general population, signs of beta cell failure with advancing age manifest not only by decreases in random insulin, but also with a corresponding increase in its precursor proinsulin. (biomedcentral.com)
  • In the Tromsø Study 1994-95 we measured insulin and proinsulin concentrations in random blood samples from 6212 persons without self-reported diabetes mellitus and plotted the levels as percentiles according to age. (biomedcentral.com)
  • In the same persons we considered the influence of age on insulin, proinsulin, and the proinsulin/insulin ratio, after adjustment for the concomitant glucose concentrations, several covariates associated with insulin resistance, and the time since the last meal. (biomedcentral.com)
  • Higher circulating proinsulin levels are associated with impaired b-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). (emory.edu)
  • Aims: Associations of proinsulin-to-insulin ratios with incident type 2 diabetes have been inconsistent. (dr-peshev.com)
  • Associations of proinsulin ratios with type 2 diabetes were determined using logistic regression and differences in prediction were assessed by comparing areas under the receiver operating characteristic curve (AROCs). (uthscsa.edu)
  • Conclusions: Proinsulin-to-C-peptide ratios were stronger predictors of diabetes in comparison with proinsulin-to-insulin ratios. (uthscsa.edu)
  • These findings support the use of C-peptide as the denominator for proinsulin ratios, to more accurately reflect the degree of disproportional hyperproinsulinaemia. (uthscsa.edu)
  • In 6212 men and women who had random measurements of insulin and proinsulin in a population-based study, and who did not report diabetes mellitus, we describe the percentiles of insulin and proinsulin levels and the proinsulin-to-insulin insulin ratio (proinsulin/insulin) according to gender and age. (biomedcentral.com)
  • This may contribute to the elevated levels of proinsulin found both at the onset of type 1 diabetes as well as in type 2 diabetes. (bioscientifica.com)
  • After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. (creativebiomart.net)
  • 2 edition of Radioimmunoassays for Insulin, C-Peptide and Proinsulin found in the catalog. (dr-peshev.com)
  • Proinsulin is normally converted to insulin and C-peptide in the beta cells. (dr-peshev.com)
  • Proinsulin levels are typically greater than 20 pmol/L. insulin and c peptide from Kevin M. Windisch MD, FAAP And Sparks Pediatric and Adolescent Medicine. (dr-peshev.com)
  • Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. (dr-peshev.com)
  • Radioimmunoassays for Insulin, C-Peptide and Proinsulin: Medicine & Health Science Books @ 5/5(1). (dr-peshev.com)
  • Read "Radioimmunoassays for Insulin, C-Peptide and Proinsulin" by L. Heding available from Rakuten Kobo. (dr-peshev.com)
  • Pancreatic extracts were found to contain equimolar amounts of insulin and C-peptide, whereas proinsulin constituted about 3% (molar) of the total IRI. (dr-peshev.com)
  • The discovery of insulin, C-peptide and proinsulin, species differences --The establishment of a radioimmunoassay --The first systematical approach --Requirements for antibodies used in RIA --Characterization of the standard substance and the substances to be measured --The tracer, characterization and limitations --Quality and reproducibility of RIA --Background for development of improved and new RIAs for insulin, C-peptide and proinsulin. (dr-peshev.com)
  • OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. (emory.edu)
  • Islets cultured at 56 mM glucose had an increased proportion of newly synthesized proinsulin when compared with islets cultured at 5.6 mM glucose after a 90-min chase periods, however, no difference was observed after culture at 11 and 28 mM glucose. (bioscientifica.com)
  • This is synthesized in the endoplasmic reticulum (ER) of pancreatic beta cells from proinsulin. (elsevier.com)
  • We use basic molecular principles and numerical simulations of time-dependent crowding conditions in the ER to show that crowding effects enhance the propensity of proinsulin molecules to (mis)fold in compressed, nonnative structures. (elsevier.com)
  • The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures. (bmj.com)
  • Proinsulin levels and proinsulin/insulin increased across age groups in both genders. (biomedcentral.com)
  • Negative associations of age with random insulin levels, together with positive associations of age with proinsulin and proinsulin/insulin, point towards a loss of beta cell function inherent in the ageing process. (biomedcentral.com)
  • Using real-time PCR, the mRNA levels of proinsulin converting enzymes (PC1 and PC2) were studied. (bioscientifica.com)
  • Transplanted mice showed high circulating proinsulin levels but, with the exclusion of those bearing curative grafts, relatively low mature insulin levels. (uthscsa.edu)
  • We conclude that a sustained functional stimulation by glucose of islets is coupled to a decreased conversion of proinsulin which is also true for islets treated with IL-1β. (bioscientifica.com)