Insulin Antibodies: Antibodies specific to INSULIN.Biphasic Insulins: An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.Bromouracil: 5-Bromo-2,4(1H,3H)-pyrimidinedione. Brominated derivative of uracil that acts as an antimetabolite, substituting for thymine in DNA. It is used mainly as an experimental mutagen, but its deoxyriboside (BROMODEOXYURIDINE) is used to treat neoplasms.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).Chlorpropamide: A sulfonylurea hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. (From Martindale, The Extra Pharmacopoeia, 30th ed, p277)Phenformin: A biguanide hypoglycemic agent with actions and uses similar to those of METFORMIN. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Insulin, Isophane: An intermediate-acting INSULIN preparation with onset time of 2 hours and duration of 24 hours. It is produced by crystallizing ZINC-insulin-PROTAMINES at neutral pH 7. Thus it is called neutral protamine Hagedorn for inventor Hans Christian Hagedorn.Antibodies: 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).Insulin Aspart: Insulin that has been modified to contain an ASPARTIC ACID instead of a PROLINE at position 38 of the B-chain.Hypoglycemia: A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.Receptor, Insulin: 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.Complement Activating Enzymes: Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.Diabetes Mellitus, Type 1: 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.Antibody Specificity: 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.Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.Antibodies, Viral: Immunoglobulins produced in response to VIRAL ANTIGENS.Diabetes Mellitus: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.Antibodies, Bacterial: Immunoglobulins produced in a response to BACTERIAL ANTIGENS.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.Insulin Resistance: Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.Antibody Formation: The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.Antibodies, Neutralizing: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Insulin Receptor Substrate Proteins: A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.Proinsulin: 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.C-Peptide: 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.Molecular Sequence Data: 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.Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects.Love: Affection; in psychiatry commonly refers to pleasure, particularly as it applies to gratifying experiences between individuals.Histamine H1 Antagonists, Non-Sedating: A class of non-sedating drugs that bind to but do not activate histamine receptors (DRUG INVERSE AGONISM), thereby blocking the actions of histamine or histamine agonists. These antihistamines represent a heterogenous group of compounds with differing chemical structures, adverse effects, distribution, and metabolism. Compared to the early (first generation) antihistamines, these non-sedating antihistamines have greater receptor specificity, lower penetration of BLOOD-BRAIN BARRIER, and are less likely to cause drowsiness or psychomotor impairment.Sister Mary Joseph's Nodule: Metastatic lesion of the UMBILICUS associated with intra-abdominal neoplasms especially of the GASTROINTESTINAL TRACT or OVARY.Umbilicus: The pit in the center of the ABDOMINAL WALL marking the point where the UMBILICAL CORD entered in the FETUS.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Blood Glucose: Glucose in blood.Nesidioblastosis: An inherited autosomal recessive syndrome characterized by the disorganized formation of new islets in the PANCREAS and CONGENITAL HYPERINSULINISM. It is due to focal hyperplasia of pancreatic ISLET CELLS budding off from the ductal structures and forming new islets of Langerhans. Mutations in the islet cells involve the potassium channel gene KCNJ11 or the ATP-binding cassette transporter gene ABCC8, both on CHROMOSOME 11.Luminescent Measurements: Techniques used for determining the values of photometric parameters of light resulting from LUMINESCENCE.Immunoassay: A technique using antibodies for identifying or quantifying a substance. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance.Luminescence: Emission of LIGHT when ELECTRONS return to the electronic ground state from an excited state and lose the energy as PHOTONS. It is sometimes called cool light in contrast to INCANDESCENCE. LUMINESCENT MEASUREMENTS take advantage of this type of light emitted from LUMINESCENT AGENTS.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Magnetics: The study of MAGNETIC PHENOMENA.Magnets: Objects that produce a magnetic field.Graves Ophthalmopathy: An autoimmune disorder of the EYE, occurring in patients with Graves disease. Subtypes include congestive (inflammation of the orbital connective tissue), myopathic (swelling and dysfunction of the extraocular muscles), and mixed congestive-myopathic ophthalmopathy.Graves Disease: A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy).Receptor, IGF Type 1: A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain.Diplopia: A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include REFRACTIVE ERRORS; STRABISMUS; OCULOMOTOR NERVE DISEASES; TROCHLEAR NERVE DISEASES; ABDUCENS NERVE DISEASES; and diseases of the BRAIN STEM and OCCIPITAL LOBE.Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.Exophthalmos: Abnormal protrusion of both eyes; may be caused by endocrine gland malfunction, malignancy, injury, or paralysis of the extrinsic muscles of the eye.Insulin Antagonists: Compounds which inhibit or antagonize the biosynthesis or action of insulin.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Kinetics: The rate dynamics in chemical or physical systems.

Frequency of islet cell autoantibodies (IA-2 and GAD) in young Brazilian type 1 diabetes patients. (1/202)

Type 1 diabetes, as an autoimmune disease, presents several islet cell-specific autoantibodies such as islet cell antibody (ICA), anti-insulin, anti-glutamic acid decarboxylase (GAD) and the antibody (Ab) against tyrosine phosphatase (PTP)-like protein known as ICA-512 (IA-2). In order to determine the frequency of the anti-GAD and anti-IA-2 autoantibodies in Brazilian type 1 diabetes patients we studied 35 diabetes mellitus (DM) type 1 patients with recent-onset disease (12 months) who were compared to 12 children with normal fasting glucose. Anti-GAD65 and anti-IA-2 autoantibodies were detected with commercial immunoprecipitation assays. The frequency of positive results in recent-onset DM type 1 patients was 80.0% for GADAb, 62.9% for IA-2Ab and 82.9% for GADAb and/or IA-2Ab. The long-duration type 1 diabetes subjects presented frequencies of 54.1% for GADAb and IA-2Ab, and 67.5% for GAD and/or IA-2 antibodies. The control group showed no positive cases. Anti-GAD and IA-2 assays showed a high frequency of positivity in these Brazilian type 1 diabetes patients, who presented the same prevalence as a Caucasian population.  (+info)

Lack of association between early childhood immunizations and beta-cell autoimmunity. (2/202)

OBJECTIVE: To determine whether early childhood immunization history affects the risk of developing the beta-cell autoimmunity that precedes type 1 diabetes. RESEARCH DESIGN AND METHODS: This article describes a case-control study whose participants were 317 children aged < or = 12 years who have a first-degree relative with type 1 diabetes. The children were enrolled in a prospective cohort study of the etiology of beta-cell autoimmunity, the Diabetes Autoimmunity Study in the Young, in Denver, Colorado. The main outcome measure was beta-cell autoimmunity as determined by persistent autoantibodies against insulin, GAD, or islet cell antibody (IA-2) 512. The number of cases with beta-cell autoimmunity was 25, and the number of control subjects (the remainder of the cohort) was 292. RESULTS: There was no difference between cases and control subjects in the proportion receiving hepatitis B (HBV), Haemophilus influenzae b (Hib), polio, or diphtheria tetanus pertussis (DTP) vaccines before 9 months of age; in the proportion receiving HBV at birth rather than later; or in the median age at first HBV, Hib, polio, or DTP vaccination. CONCLUSIONS: The results suggest that changing the early childhood immunization schedule would not affect the risk of developing beta-cell autoimmunity or type 1 diabetes.  (+info)

Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study. (3/202)

OBJECTIVE: We undertook this study to test whether Bacillus Calmette-Guerin (BCG) vaccine preserves beta-cell function and increases the remission rate in children with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized double-blind placebo-controlled trial offered to children referred to the Barbara Davis Center for Childhood Diabetes or the Baystate Medical Center with a diagnosis of new-onset type 1 diabetes. There were 94 children aged 5-18 years who received either BCG or saline intradermally within 4 months of onset of symptoms and who were then evaluated at 3-month intervals for 2 years. The primary end point was remission, defined as insulin independence for 4 weeks. Secondary end points were C-peptide levels (fasting and in response to a mixed meal challenge), insulin dose, and HbA1c. RESULTS: Of the patients, 47 were randomized to each arm; 7 in the placebo group and 9 in the BCG group did not complete 1 year of the study and are not included in the analysis. One patient from each group achieved remission. Fasting and stimulated C-peptide levels did not differ by treatment arm but declined in both groups and were lower initially and during the entire 2-year period in younger children. Insulin requirements and HbA1c levels did not differ in the two groups. CONCLUSIONS: Vaccination with BCG at the time of onset of type 1 diabetes does not increase the remission rate or preserve beta-cell function.  (+info)

Early expression of antiinsulin autoantibodies of humans and the NOD mouse: evidence for early determination of subsequent diabetes. (4/202)

With the development of an insulin autoantibody (IAA) assay performed in 96-well filtration plates, we have evaluated prospectively the development of IAA in NOD mice (from 4 weeks of age) and children (from 7 to 10 months of age) at genetic risk for the development of type 1 diabetes. NOD mice had heterogeneous expression of IAA despite being inbred. IAA reached a peak between 8 and 16 weeks and then declined. IAA expression by NOD mice at 8 weeks of age was strongly associated with early development of diabetes, which occurred at 16-18 weeks of age (NOD mice IAA(+) at 8 weeks: 83% (5/6) diabetic by 18 weeks versus 11% (1/9) of IAA negative at 8 weeks; P <.01). In man, IAA was frequently present as early as 9 months of age, the first sampling time. Of five children found to have persistent IAA before 1 year of age, four have progressed to diabetes (all before 3.5 years of age) and the fifth is currently less than age 2. Of the 929 children not expressing persistent IAA before age 1, only one has progressed to diabetes to date (age onset 3), and this child expressed IAA at his second visit (age 1.1). In new onset patients, the highest levels of IAA correlated with an earlier age of diabetes onset. Our data suggest that the program for developing diabetes of NOD mice and humans is relatively "fixed" early in life and, for NOD mice, a high risk of early development of diabetes is often determined by 8 weeks of age. With such early determination of high risk of progression to diabetes, immunologic therapies in humans may need to be tested in children before the development of IAA for maximal efficacy.  (+info)

Antibody-mediated insulin resistance treated by cessation of insulin administration. (5/202)

A 45-year-old Japanese man was referred to our hospital because of hyperglycemia despite the administration of as much as 120 U/day of human insulin. He had no history of injecting animal insulin. Free insulin was below 5 microU/ml, but a high titer of total insulin (about 3,000 microU/ml) was observed, suggesting the presence of antibodies against human insulin. Scatchard analysis showed an increased insulin binding capacity in the plasma characterized by a higher affinity for insulin. He was successfully treated by cessation of insulin administration. A Scatchard analysis series showed that a reduction in the insulin binding capacity of antibodies paralleled the improvement in glycemic control.  (+info)

Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. (6/202)

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children.  (+info)

Immunoreactive somatostatin is present in discrete cells of the endocrine pancreas. (7/202)

A discrete population of cells of the endocrine pancreas contains immunoreactive somatostatin as shown by immunofluorescence. These cells are different from those containing glucagon or insulin. This unexpected observation may be of physiopathological significance in the regulatory mechanisms involved in the secretion of glucagon and insulin.  (+info)

Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry. (8/202)

OBJECTIVE: To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual beta-cell function noted in some, but not all, patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients <40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years. RESULTS: Two years after diagnosis, random C-peptide levels had decreased significantly (P < 0.001) in ICA+ patients but not in ICA- patients. C-peptide values <50 pmol/ were noted in 88% of patients diagnosed before 7 years of age, in 45% of patients diagnosed between ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P < 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (> or =50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in patients with lower ICA titers, P < 0.001). In patients diagnosed after 15 years of age, 36% of patients with ICA titers > or =12JDF units developed low C-peptide levels compared with 14% of patients with ICA titers < 12 JDF units (P < 0.03). Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P < 0.001) and to a lesser degree positively correlated with age at diagnosis (P < 0.02), regardless of the levels or number of molecular autoantibodies. CONCLUSIONS: Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual beta-cell function. Using these selection criteria, it is possible to better target beta-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The ICA assay measures clinically relevant antibodies not detected in antibody assays that use recombinant human autoantigens for substrate.  (+info)

  • It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. (
  • Several potentially pathogenic islet/β cell autoantigens have been identified by their reactivity with circulating antibodies or T cells in rodents and humans with subclinical or clinical IDDM, particularly insulin, glutamic acid decarboxylase (GAD), and a tyrosine phosphatase, IA-2 ( 9 ). (
  • When we administered insulin aerosol to NOD mice after the onset of subclinical disease, pancreatic islet pathology and diabetes incidence were both significantly reduced. (
  • Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM: (
  • MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. (
  • Insulin is an autoantigen in humans and nonobese diabetic (NOD) mice with insulindependent diabetes mellitus (IDDM). (
  • The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 γδ T cells. (
  • Insulin-treated mice had increased circulating antibodies to insulin, absent splenocyte proliferation to the major epitope, insulin B chain amino acids 9-23, which was associated with increased IL-4 and particularly IL-10 secretion, and reduced proliferation to glutamic acid decarboxylase, another islet autoantigen. (
  • IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. (
  • Induction of regulatory CD8 γδ T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM. (
  • Antibodies are proteins the body produces to protect itself when it detects anything "foreign," such as a virus or transplanted organ. (
  • Search, Find and Buy Antibodies, ELISA Kits and Proteins. (
  • Three adapter proteins, IRS1, IRS2 and Shc, become phosphorylated on tyrosine residues following insulin receptor activation. (
  • The specificities of the antibodies were investigated by using binding assays with different insulinoma subcellular fractions, by indirect immunofluorescence studies with intact and permeabilized cells, and by immunoblotting of granule membrane proteins fractionated by SDS/polyacrylamide-gel electrophoresis. (
  • Biosynthesis of insulin secretory granule membrane proteins. (
  • Affinity chromatography is an efficient method to isolate proteins by taking advantage of their affinities for specific molecules such as substrates, inhibitors, antigens, ligands, antibodies, and other interacting molecules, including subunits. (
  • Later in my career, I used commercially available affinity columns and beads, which specifically bind to tags or fusion proteins designed for purification of antibodies and recombinant proteins (Table 1 ) ( 6 - 11 ). (
  • The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. (
  • Check out links to articles that cite our custom service antibodies, peptides, and proteins in major peer-reviewed journals, organized by research category. (
  • Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. (
  • Synthetic peptides, native or recombinant proteins can be used for medical, academic and research purposes, such as gene therapy, drug screening, antibody production, cell function analysis. (
  • The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. (
  • Antibodies are useful not only to detect specific biomolecules but also to measure changes in their level and specificity of modification by processes such as phosphorylation, methylation, or glycosylation. (
  • Insulin decreases blood glucose concentration. (
  • IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. (
  • Insulin enhances membrane transport of glucose, amino acids, and certain ions. (
  • Her plasma glucose was 40 mg/dl, insulin 103.7 μU/ml, and C-peptide 4.1 ng/ml. (
  • antibody to beef insulin when injected into mice produced as many convulsions and lowered the blood glucose to the same mean level as did 50 mU. (
  • antibody did not convulse and had a mean blood glucose of 108 mg./100 ml. (
  • Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. (
  • Thus, we set out to define the clinical characteristics of these patients who generated IAs and manifested unexplainable fluctuations in blood glucose levels while receiving insulin analogs and to determine how best to treat them. (
  • Insulin is a pancreatic hormone that regulates glucose uptake and the synthesis of protein and fat. (
  • CONCLUSIONS - The lower fasting free/total IRI ratio and greater increase in glucose and total IRI in response to Sustacal in the hypo-high group compared with either the hypo-flat or control groups are consistent with the presence of significant quantities of anti-insulin antibodies in the hypo-high group. (
  • This leads to higher insulin levels and more rapid tissueassimilation of glucose followed by a decline in the insulin level as the glucose level subsides. (
  • Most pets are prescribed long acting insulin medication that controls blood glucose for a longer period of time. (
  • Lab tests include the plasma glucose level, the fasting insulin level, and a lipid profile, among others. (
  • [ 12 ] Given that glucose and lipid metabolism largely depend on mitochondria to generate energy in cells, mitochondrial dysfunction may play an important role in the development of insulin resistance and associated complications. (
  • These data demonstrated otelixizumab's ability to preserve beta cell function, as measured by C-peptide, in patients up to 18 months after dosing, as well as reduce the need for delivered insulin to maintain glucose control. (
  • The trial was designed to evaluate whether a single course of otelixizumab, administered not more than 90 days after the initial diagnosis, would reduce the amount of administered insulin required to control blood glucose levels by inhibiting the destruction of beta cells. (
  • Abgent's experienced staff custom validates more than 1,000 antibodies each month in Western Blot (WB), Immunofluorescence (IF), Immunohistochemistry (IHC), Flow Cytometry (FC) and additional applications. (
  • The most potent neutralizer, IgG1 m610, inhibited phosphorylation of the IGF-IR and the insulin receptor, as well as phosphorylation of the downstream kinases Akt and mitogen-activated protein kinase with an IC 50 of the order of 1 nmol/L at IGF-II concentration of 10 nmol/L. It also inhibited growth of the prostate cancer cell line DU145 and migration of the breast cancer line cells MCF-7. (
  • Although IR-A and IR-B have similar affinities for insulin, IR-A exhibits higher affinity for IGF-II than IR-B ( 21 ). (
  • They bound with high (subnanomolar) affinity to IGF-II, did not cross-react with IGF-I and insulin, and potently inhibited signal transduction mediated by the IGF-IR interaction with IGF-II. (
  • 2 - 5 The IAs of these patients have a lower affinity and a higher binding capacity than those from patients with insulin autoimmune syndrome (IAS) 6 or those who do not develop hypoglycemia when treated with insulin. (
  • Ambient insulin levels, various physiologic and disease states, and drugs regulate insulin receptor concentration or affinity. (
  • Antibodies in 3 diabetic patients and 7 non-diabetic control subjects were purified using protein-G sepharose affinity column chromatography and S-300 gel filtration methods purity of the IgG antibodies was confirmed by SDS-PAGE and in western blot analysis and proteolytic activity of electrophoretically homogenous IgG antibodies was confirmed with zymogram analysis. (
  • The most specific and sensitive of these, the antiendomysial antibody, is the indirect immunofluorescence test which uses monkey esophagus smooth muscle as substrate. (
  • Burch HB, Clement S, Sokol MS, Landry F: Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review. (
  • Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinaemic hypoglycaemia, whose prevalence is higher in East Asian populations due to the higher prevalence of specific immunogenetic determinants. (