TY - JOUR. T1 - Insulin receptor phosphorylation may not be a prerequisite for acute insulin action. AU - Simpson, Ian A.. AU - Hedo, José A.. PY - 1984/1/1. Y1 - 1984/1/1. N2 - An antiserum to the insulin receptor mimicked insulins acute actions on glucose transport, phosphorylation of integral membrane proteins, and internalization of the insulin receptor in isolated rat adipose cells. These insulinomimetic actions of the antiserum occurred without the equivalent increase in phosphorylation of the β subunit of the insulin receptor observed with insulin. Thus, a role of receptor phosphorylation in acute insulin action is now questioned.. AB - An antiserum to the insulin receptor mimicked insulins acute actions on glucose transport, phosphorylation of integral membrane proteins, and internalization of the insulin receptor in isolated rat adipose cells. These insulinomimetic actions of the antiserum occurred without the equivalent increase in phosphorylation of the β subunit of the insulin ...

We have developed a radioimmunoassay for human insulin receptor. Serum from a patient with Type B severe insulin resistance was used as anti-insulin receptor antiserum. Pure human placental insulin receptor was used as reference preparation and 125I labeled pure insulin receptor as trace. The radioimmunoassay was sensitive (limit of detection less than 17 fmol), reproducible (inter and intra-assay coefficients of variation 12.5% and 1.6% respectively) and specific (no crossreactivity with pure placental IGF-1 receptor, insulin and glucagon). The anti-insulin receptor antibody was, however, able to differentiate between insulin receptor from human placenta and from rat liver. To determine the number of insulin binding sites per receptor, we measured insulin binding (by insulin binding assay) and insulin receptor mass (by radioimmunoassay) in solubilized aliquots from 5 human placentas. The molar ratio of insulin binding to receptor mass was 0.86 +/- 0.12 when binding was determined with

Insulin is obtained from pork pancreas or is made chemically identical to human insulin by recombinant DNA technology or chemical modification of pork insulin. Insulin analogs have been developed by modifying the amino acid sequence of the insulin molecule.. Insulin is available in rapid-, short-, intermediate-, and long-acting types that may be injected separately or mixed in the same syringe. Rapid-acting insulin analogs (insulin lispro and insulin aspart) are available, and other analogs are in development. Regular is a short-acting insulin. Intermediate-acting insulins include lente and NPH. Ultralente and insulin glargine are long-acting insulins. Insulin preparations with a predetermined proportion of intermediate-acting insulin mixed with short- or rapid-acting insulin (e.g., 70% NPH/30% regular, 50% NPH/50% regular, and 75% NPL/25% insulin lispro) are available.. Different companies have adopted different names for the same short-, intermediate-, or long-acting types of insulin or their ...

Background: To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods: This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results: We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was ...

A series of studies is described in which specific and conventional insulin immunoassays, the hyperinsulinaemic clamp technique and forearm venous occlusion plethysmography with local intra-arterial infusions have been used to investigate: the effect of insulin assay specificity on the relationships among serum insulin concentrations, insulin sensitivity, and blood pressure in diabetic and non-diabetic subjects with and without essential hypertension (Chapter 5) the effect of sustained physiological activation of the renin-angiotensin system induced by moderate dietary sodium restriction on insulin sensitivity in patients with non-insulin-dependent diabetes mellitus (Chapter 6) the relationship between endothelial function and insulin sensitivity in healthy subjects (Chapter 7) Prior to these investigations, preliminary studies (Chapters 3 and 4) were performed in order to validate aspects of the clinical physiological techniques required for the measurement of blood flow and insulin ...

TY - JOUR. T1 - Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans. AU - Bajaj, Mandeep. AU - Berria, Rachele. AU - Pratipanawatr, Thongchai. AU - Kashyap, Sangeeta. AU - Pratipanawatr, Wilailak. AU - Belfort, Renata. AU - Cusi, Kenneth. AU - Mandarino, Lawrence. AU - Defronzo, Ralph A.. PY - 2002. Y1 - 2002. N2 - To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 ± 4 yr; body mass index, 27.4 ± 1.2 kg/m2; fasting plasma glucose, 5.2 ± 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU·m-2·min-1) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin ...

Chronic insulin treatment in both cell lines (C2C12 and Huh7) causes a decrease in phosphorylation of Akt, which is a hallmark of insulin resistance at the cellular level. The same effect was observed in both cell lines after chronic palmitate treatment. Chronic insulin treatment does not affect viability of (C2C12 and Huh7), while palmitate treatment decreases cell viability in both cell types. Chronic insulin treatment does not affect mitochondrial respiration, at variance with chronic palmitate treatment, which decreases respiration in C2C12 and Huh7 cells. However, chronic insulin treatment causes a decrease in respiratory acceptor control ratio (RCR) in C2C12, as observed with palmitate treatment. This is not the case for Huh7 cells, where RCR is unchanged after insulin treatment, while lowered only after palmitate treatment. Total ROS production does not change significantly in either cell line. Both C2C12 and Huh7 cells showed preserved mitochondrial morphology after chronic insulin ...

TY - JOUR. T1 - Dose-response characteristics for effects of insulin on production and utilization of glucose in man.. AU - Rizza, R. A.. AU - Mandarino, L. J.. AU - Gerich, J. E.. PY - 1981/6/1. Y1 - 1981/6/1. N2 - To determine the dose-response characteristics for the effects of insulin on glucose production, glucose utilization, and overall glucose metabolism in normal man, 15 healthy subjects were infused with insulin for 8 h at sequential rates ranging from 0.2 to 5.0 mU.kg-1.min-1; each rate was used for 2 h. Glucose production and utilization were measured isotopically ([3-3H]glucose). Tissue insulin receptor occupancy was estimated from erythrocyte insulin binding. Glucose production was completely suppressed at plasma insulin concentrations of approximately 60 microunits/ml. Maximal glucose utilization (10-11 mg.kg-1.min-1) occurred at insulin concentrations of 200-700 microunits/ml. The concentration of insulin causing half-maximal glucose utilization (55 + 7 microunits/ml) was ...

TY - JOUR. T1 - Membrane-targeted phosphatidylinositol 3-kinase mimics insulin actions and induces a state of cellular insulin resistance. AU - Egawa, Katsuya. AU - Sharma, Prem M.. AU - Nakashima, Naoki. AU - Huang, Yi. AU - Huver, Evana. AU - Boss, Gerry R.. AU - Olefsky, Jerrold M.. PY - 1999/5/14. Y1 - 1999/5/14. N2 - Phosphatidylinositol (PI) 3-kinase plays an important role in various insulin-stimulated biological responses including glucose transport, glycogen synthesis, and protein synthesis. However, the molecular link between PI 3- kinase and these biological responses is still unclear. We have investigated whether targeting of the catalytic p110 subunit of PI 3-kinase to cellular membranes is sufficient and necessary to induce PI 3-kinase dependent signaling responses, characteristic of insulin action. We overexpressed Myc- tagged, membrane-targeted p110 (p110(CAAX)), and wild-type p110 (p110(WT)) in 3T3-L1 adipocytes by adenovirus-mediated gene transfer. Overexpressed p110(CAAX) ...

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Microtubules - cellular highways that deliver cargo to the cell membrane for secretion - have a surprising role in pancreatic beta cells. Instead of facilitating glucose-stimulated insulin secretion, they limit it, a team of Vanderbilt investigators reported recently in Developmental Cell.. The findings reveal that microtubules act as a cellular rheostat to precisely control insulin secretion and suggest that disturbance of this control may contribute to beta cell dysfunction and type 2 diabetes. Targeting the microtubule regulation of insulin secretion may offer new ways to treat diabetes.. Irina Kaverina, Ph.D., Xiadong Zhu, Ph.D., and colleagues began using pancreatic beta cells as a model to study microtubule function - to explore how microtubules traffic cargo such as insulin granules from the cell interior to the periphery.. In their initial studies, the researchers used compounds to destroy the microtubules, then stimulated the pancreatic islets with glucose and measured how much ...

We assessed whether insulin sensitivity improved after renal denervation (RDN) for resistant hypertension. Twenty-three patients underwent a two-step hyperinsulinemic euglycemic clamp (HEC) with glucose tracer and labeled glucose infusion and oral glucose tolerance test (OGTT) before and 6 months after RDN. Eighteen patients had metabolic syndrome at baseline. Blood pressure declined significantly after RDN whereas fasting plasma glucose (5.9 ± 0.7 mmol/L), insulin (254 (88-797) pmol/L), C- peptide (2.4 (0.9-5.7) nmol/L) remained unchanged. Endogenous glucose release during HEC was less suppressed after RDN, suggesting a slight decrease in hepatic insulin sensitivity. During high-dose insulin infusion, whole-body glucose disposal was low and remained unchanged after RDN, indicating persistent peripheral insulin resistance. Area under the curve 0-120min for glucose and insulin during OGTT, Quantitative Insulin Sensitivity Check Index, Simple Index assessing Insulin Sensitivity oral glucose ...

TY - JOUR. T1 - The in vivo interaction between gliclazide and glibenclamide and insulin on glucose disposal in the rat. AU - Tanira, Musbah O M. AU - Furman, Brian L.. PY - 1999/5. Y1 - 1999/5. N2 - Many reports suggest that extrapancreatic actions contribute to the antidiabetic effect of sulphonylurea drugs (SUs). In this work, the ability of two SUs, namely, gliclazide and glibenclamide, to augment insulin action was studied in vivo. Both drugs elevated the plasma concentration of immunoreactive insulin (IRI) and lowered the plasma concentrations of glucose and non-esterified fatty acids (NEFA) in normal intact rats. These changes were not reproduced in alloxan-diabetic or eviscerated rats. The actions of insulin on plasma glucose and NEFA were not augmented by gliclazide in alloxan-diabetic rats. Neither gliclazide nor glibenclamide (given acutely and for 30 days) augmented the actions of exogenously administered insulin in reducing plasma glucose or NEFA concentrations in intact or ...

TY - JOUR. T1 - A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 - the functional significance of L-alanine. AU - Dixon, G. AU - Nolan, J. AU - McClenaghan, Neville. AU - Flatt, Peter. AU - Newsholme, P. PY - 2003/12. Y1 - 2003/12. N2 - Evidence has been published that L-alanine may, under appropriate conditions, promote insulin secretion in normal rodent islets and various beta cell lines. Previous results utilising the clonal beta-cell line BRIN-BD11, demonstrated that alanine dramatically elevated insulin release by a mechanism requiring oxidative metabolism. We demonstrate in this paper that addition Of L-alanine had an insulinotropic effect in dispersed primary islet cells. Addition Of D-glucose increased L-alanine consumption in both BRIN-BD11 cells and primary islet cells. L-glutamine consumption in the BRIN-BD11 cell line and primary rat islets was also determined. The consumption rate was in line with that previously reported for ...

TY - JOUR. T1 - Pathophysiology of hyperinsulinemia following pancreas transplantation. T2 - Altered pulsatile versus basal insulin secretion and the role of specific transplant anatomy in dogs. AU - Earnhardt, Richard C.. AU - Veldhuis, Johannes D. AU - Cornett, Greg. AU - Hanks, John B.. AU - Andersen, Dana K.. AU - Brunicardi, F. Charles. AU - Thomas, Francis T.. AU - Najarian, John S.. PY - 2002/10. Y1 - 2002/10. N2 - Objective: To evaluate the effect of the anatomical alterations of the pancreas required for transplantation on pulsatile insulin secretion. Summary Background Data: Pancreas transplantation involves anatomical changes that have unknown consequences on glucose homeostasis. Pancreas transplant patients are free of exogenous insulin requirements, yet appear to have endogenous hyperinsulinemia. The effect of surgical alterations on posttransplant insulin release is not completely known, specifically with regards to possible alterations in patterns of pulsatile release. Methods: ...

As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimers disease, numerous studies have emphasized the importance of insulin in learning and memory processes. This has been further supported by work showing that intranasal delivery of insulin can enhance insulin receptor signaling, alter cerebral blood flow, and improve memory recall. Additionally, inhibition of insulin receptor function or expression using molecular techniques has been associated with reduced learning. Here, we sought a different approach to increase insulin receptor activity without the need for administering the ligand. A constitutively active, modified human insulin receptor (IRβ) was delivered to the hippocampus of young (2 months) and aged (18 months) male Fischer 344 rats in vivo. The impact of increasing hippocampal insulin receptor expression was investigated using several outcome ...

Accumulated evidence suggests that hydrogen peroxide (H2O2) generated in cells during insulin stimulation plays an integral role in insulin receptor signal transduction. The role of insulin-induced H2O2 in neuronal insulin receptor activation and the origin of insulin-induced H2O2 in neurons remain unclear. The aim of the present study is to test the following hypotheses (1) whether insulin-induced H2O2 is required for insulin receptor autophosphorylation in neurons, and (2) whether mitochondrial respiratory chain is involved in insulin-stimulated H2O2 production, thus playing an integral role in insulin receptor autophosphorylation in neurons. Insulin stimulation elicited rapid insulin receptor autophosphorylation accompanied by an increase in H2O2 release from cultured cerebellar granule neurons (CGN). N-acetylcysteine (NAC), a H2O2 scavenger, inhibited both insulin-stimulated H2O2 release and insulin-stimulated autophosphorylation of insulin receptor. Inhibitors of respiratory chain-mediated H2O2

TY - JOUR. T1 - SAD-A Potentiates Glucose-Stimulated Insulin Secretion as a Mediator of Glucagon-Like Peptide 1 Response in Pancreatic β Cells. AU - Nie, Jia. AU - Lilley, Brendan N.. AU - Pan, Y. Albert. AU - Faruque, Omar. AU - Liu, Xiaolei. AU - Zhang, Weiping. AU - Sanes, Joshua R.. AU - Han, Xiao. PY - 2013/7/1. Y1 - 2013/7/1. N2 - Type 2 diabetes is characterized by defective glucose-stimulated insulin secretion (GSIS) from pancreatic cells, which can be restored by glucagon-like peptide 1 (GLP-1), an incretin hormone commonly used for the treatment of type 2 diabetes. However, molecular mechanisms by which GLP-1 affects glucose responsiveness in islet β cells remain poorly understood. Here we investigated a role of SAD-A, an AMP-activated protein kinase (AMPK)-related kinase, in regulating GSIS in mice with conditional SAD-A deletion. We show that selective deletion of SAD-A in pancreas impaired incretins effect on GSIS, leading to glucose intolerance. Conversely, overexpression of ...

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OBJECTIVE-To evaluate whether treatment with insulin is advantageous compared with oral antidiabetes agents in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy.. RESEARCH DESIGN AND METHODS-Newly diagnosed type 2 diabetic patients with severe hyperglycemia were hospitalized and treated with intensive insulin injections for 10-14 days. The oral glucose tolerance test (OGTT) was performed after intensive insulin treatment. After discharge, the patients were randomized to receive either insulin injections or oral antidiabetes drugs (OADs) for further management. The OGTT was repeated 6 months later, and β-cell function and insulin sensitivity were evaluated again. These subjects were continually followed up for another 6 months to evaluate their long-term glycemic control.. RESULTS-At the 6th month of the study, the A1C level was significantly lower in the insulin group than in the OAD group (6.33 ± 0.70% vs. 7.50 ± 1.50%; P = 0.002). During ...

Patients were randomly assigned, using a 1:1 block randomization scheme, to either the experimental protocol using a continuous insulin infusion (CII) protocol (1) or to the control group using a standard intermittent sliding-scale insulin bolus (IIB) protocol (2). In the CII regimen, the target blood glucose concentration was 100-150 mg/dl. If blood glucose levels exceeded 150 mg/dl, a continuous insulin infusion was initiated. Adjustments to the insulin infusion were determined by both the current blood glucose concentrations and insulin infusion rates and as specified in 1. Changes in the insulin infusion rate were made by the anesthesiologist in the operating room and by the patients nurse in the postanesthetic care unit and vascular intensive care unit. This protocol had previously been evaluated and shown to achieve blood glucose concentrations within the target range in more than 70% of patients.9 Blood glucose levels were measured in the CII group every hour until stable. Blood glucose ...

Objective: Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatment improves insulin sensitivity and exercise capacity in obese insulin resistant mice and whether skeletal muscle AMPK was important for mediating potential effects. Methods: Glucose homeostasis, insulin sensitivity, exercise capacity, and electron transport chain content/activity were examined in wildtype (WT) and AMPK β1β2 muscle-specific null (AMPK-MKO) mice fed a high-fat diet (HFD) with or without R419 supplementation. Results: There was no change in weight gain, adiposity, glucose tolerance or insulin sensitivity between HFD-fed WT and AMPK-MKO mice. In both HFD-fed WT and AMPK-MKO mice, R419 enhanced insulin tolerance, insulin-stimulated glucose disposal, skeletal muscle ...

Fetal rat pancreatic cells were isolated from pancreatic primordia on days 12-14 of pregnancy and cultured for 48 h in the presence of 5 mmol/l glucose. Insulin accumulation in the medium over the next 24 h was measured. Cultured cells from day 12 fetuses secreted about 1 fmol insulin per pancreas in response to 5 or 15 mmol/l glucose irrespective of whether 1 mmol/l tolbutamide, 400 mumol/l diazoxide, 5 mmol/l theophylline or 10 mmol/l mannoheptulose was present. In contrast, insulin released from day 13 cultured cells increased significantly from 3.0 +/- 0.6 to 6.2 +/- 2.2 fmol per pancreas, when the glucose concentration was raised. Tolbutamide increased, diazoxide and mannoheptulose decreased and theophylline had no effect on insulin release. Even more pronounced effects were found on insulin release from day 14 cultured cells, in which theophylline also increased the release. In addition, insulin release from cells from pregnancy day 14 was 75 +/- 16 amol/min per pancreas when the cells ...

The effect of xylazine and xylazine followed 20 minutes later by insulin upon glucose metabolism and plasma insulin concentrations was examined in three cows. After doses of 0.18 mg per kg xylazine given intramuscularly (IM) or 0.15 mg per kg given intravenously (IV) hepatic glucose production increased, plasma insulin concentrations decreased to 25 to 33 per cent of control values, and there was a prolonged hyperglycaemia. When 200 units of soluble insulin were given 20 minutes after similar doses of xylazine there was a rapid fall in blood glucose and a reduction in the rate of glucose production by the liver. Xylazine-induced hyperglycaemia arose from a combination of increased hepatic glucose production and reduced plasma insulin concentrations. Peripheral tissues were still responsive to insulin and when adequate insulin was available blood glucose concentrations rapidly decreased.. ...

New Insulin Analog The first of possibly 2 new insulin analogs to be introduced this year was approved by the FDA in late April. Insulin glargine is an insulin analog produced by recombinant DNA technology. A glycine substitution on the A-chain and the extension on the B-chain of 2 arginine residues creates a shift in the isoeletric point, reducing the aqueous solubility of this insulin at physiologic pH. Furthermore, the hexomeric structure of this molecule is stabilized which causes a delay in the dissociation into monomers. Consequently, insulin glargine has a delayed and prolonged absorption.The absorption of insulin glargine is flat and lasts 24 hours. Perhaps even more importantly, the absorption is more consistent, compared with the other commonly used basal insulins, NPH and Ultralente. The need to separate basal from prandial insulins will continue to become more important as insulin therapies for type 1 diabetes continues to evolve.Studies for insulin glargine show 1 common theme -- a ...

TY - JOUR. T1 - Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS). AU - Dunaif, Andrea. AU - Wu, Xinqi. AU - Lee, Anna. AU - Diamanti-Kandarakis, Evanthia. PY - 2001/8/27. Y1 - 2001/8/27. N2 - Women with polycystic ovary syndrome (PCOS) are insulin resistant secondary to a postbinding defect in insulin signaling. Sequential euglycemic glucose clamp studies at 40 and 400 mU·m-2·min-1 insulin doses with serial skeletal muscle biopsies were performed in PCOS and age-, weight-, and ethnicity-matched control women. Steady-state insulin levels did not differ, but insulin-mediated glucose disposal was significantly decreased in PCOS women (P , 0.05). Insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI 3K) activity was significantly decreased in PCOS (n = 12) compared with control skeletal muscle (n = 8; P , 0.05). There was no significant difference in the abundance of IR, IRS-1, or the p85 regulatory subunit of PI 3K in PCOS (n = 14) ...

TY - JOUR. T1 - Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects. AU - Koffler, Michael. AU - Raskin, Philip. AU - Womble, Debra. AU - Helderman, J. Harold. PY - 1991/1/1. Y1 - 1991/1/1. N2 - Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in ...

We previously have shown that during the transition from NGT to IGT to T2DM, β-cell function progressively declines and peripheral insulin resistance progressively increases (31,35). Adipo-IR also is increased in patients with T2DM, but the natural history of its development as individuals progress from NGT to IGT to T2DM has been poorly studied. As recently reviewed (21), a number of indices of adipocyte insulin resistance have been proposed that are based on tracer turnover (i.e., labeled palmitate or glycerol) or FFA suppression during insulin infusion (euglycemic-hyperinsulinemic clamp) or OGTT. In the current study, we used the product of fasting plasma FFA and fasting plasma insulin concentrations as the index of Adipo-IR. Because the circulating plasma FFA concentration closely reflects the rate of peripheral lipolysis, Adipo-IR represents an index for adipose tissue resistance to the antilipolytic effect of insulin. The hyperbolic relationship between plasma insulin and FFA ...

Background: Type 2 diabetes mellitus (T2DM) is a progressive disorder of β-cell dysfunction until majority of patients with a longer duration of diabetes remain poorly controlled with oral agents, and use of insulin, which could improve glycemic control .Guidelines from the American Diabetes Association and the European Association for the Study of Diabetes recommend that insulin secretagogues such as sulfonylureas be discontinued at the time of insulin initiation to reduce the risk of hypoglycemia, and that treatment be intensified if HbA1c levels remain above-target 3 months after insulin initiation. Study design and methods: It was a prospective study and patients diagnosed with T2DM initiating insulin and no prior insulin use. The study duration was six months (December 2016 to May 2017) among type 2 diabetes mellitus patients at Karuna Medical College and Hospital, Diabetic centre, Quality clinic-Palakkad. Result and Discussion: Out of total 308 study populations, 226(73.37%) were taking ...

TY - JOUR. T1 - Do low glycemic index diets increase insulin sensitivity in overweight or obese patients?. AU - Jana, Kyu. PY - 2016/12/1. Y1 - 2016/12/1. N2 - Among overweight or obese patients without diabetes mellitus, lower glycemic index (GI) diets alone do not improve insulin sensitivity. However, low GI diets combined with high-intensity exercise do improve insulin sensitivity (SOR: C, trials using disease-oriented outcomes).. AB - Among overweight or obese patients without diabetes mellitus, lower glycemic index (GI) diets alone do not improve insulin sensitivity. However, low GI diets combined with high-intensity exercise do improve insulin sensitivity (SOR: C, trials using disease-oriented outcomes).. UR - http://www.scopus.com/inward/record.url?scp=85050716267&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=85050716267&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:85050716267. VL - 19. SP - E12. JO - Evidence-Based Practice. JF - Evidence-Based Practice. SN - ...

The purpose of this study is to compare the change in glycemic control, as measured by hemoglobin A1c (HbA1c) from baseline to study week 24, in subjects receiving insulin glulisine as mealtime insulin following a variable bolus insulin regimen (based on carbohydrate counting) versus a fixed bolus insulin regimen, with insulin glargine as basal insulin in both arms of the study ...

TY - JOUR. T1 - Correction of hyperglycemia with phlorizin normalizes tissues sensitivity to insulin in diabetic rats. AU - Rossetti, L.. AU - Smith, D.. AU - Shulman, G. I.. AU - Papachristou, D.. AU - DeFronzo, R. A.. PY - 1987. Y1 - 1987. N2 - Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with phlorizin to normalize glucose tolerance; group IV, phlorizin-treated controls; and group V, phlorizin-treated diabetic rats restudied after discontinuation of phlorizin. Insulin sensitivity was assessed with the euglyemic hyperinsulinemic clamp technique in awake, unstressed rats. Insulin-mediated glucose metabolism was ...

Among adult patients diagnosed with type 2 diabetes, about 6% have autoantibodies directed against the insulin producing beta cells in the pancreas. These patients have a progressive beta cell destruction and most of them will be insulin dependent within 3-5 yrs. Patients with this latent autoimmune diabetes in adults (LADA) have a considerable remaining beta cell mass at diagnosis, and are suitable for evaluating new therapies for autoimmune diabetes Animal studies in diabetes prone mice have demonstrated potential positive effects of early insulin treatment, with a lower incidence of diabetes or a delay before diagnosis. The aim of this study was to investigate the effect of early insulin treatment of LADA patients, in respect to residual beta-cell function and metabolic control, compared to a group who were conventionally treated with diet and/or oral hypoglycaemic agents (OHA) and insulin not before it was clinically needed ...

1. The effects of glucose on insulin secretion and Rb-86 efflux from isolated rat islets were studied at six different times during a 24-h period (00.00, 04.00, 08.00, 12.00, 16.00 and 20.00 h), 2. In the absence of glucose and in the presence of substimulatory concentrations (2.8 mmol/L) of the sugar, insulin secretion did not vary with the time of day. At a glucose concentration of 5.6 mmol/L the stimulated insulin secretion was greater than basal levels only at 20.00 h, 3. At a higher sugar concentration (8.3 mmol/L) the increase in insulin secretion and the reduction in Rb-86 efflux rate were more marked during the dark period. No effect of the time of day on insulin secretion was observed at glucose concentrations above 8.3 mmol/L (except in 27.7 mmol/L), 4. The time of day appears to affect insulin secretion mainly at glucose concentrations close to physiological values (5.6-8.3 mmol/L), 5. This result agrees with the ability of physiological amounts of glucose to alter the ...

To elucidate cellular mechanisms of insulin resistance induced by excess dietary fat, we studied conscious chronically high-fat-fed (HFF) and control chow diet-fed rats during euglycemic-hyperinsulinemic (560 pmol/l plasma insulin) clamps. Compared with chow diet feeding, fat feeding significantly impaired insulin action (reduced whole body glucose disposal rate, reduced skeletal muscle glucose metabolism, and decreased insulin suppressibility of hepatic glucose production [HGP]). In HFF rats, hyperinsulinemia significantly suppressed circulating free fatty acids but not the intracellular availability of fatty acid in skeletal muscle (long chain fatty acyl-CoA esters remained at 230% above control levels). In HFF animals, acute blockade of beta-oxidation using etomoxir increased insulin-stimulated muscle glucose uptake, via a selective increase in the component directed to glycolysis, but did not reverse the defect in net glycogen synthesis or glycogen synthase. In clamp HFF animals, etomoxir did not

Insulin degludec (INN/USAN) is an ultralong-acting basal insulin analogue that was developed by Novo Nordisk under the brand name Tresiba. It is administered via subcutaneous injection once daily to help control the blood sugar level of those with diabetes. It has a duration of action that lasts up to 42 hours (compared to 18 to 26 hours provided by other marketed long-acting insulins such as insulin glargine and insulin detemir), making it a once-daily basal insulin, that is one that provides a base insulin level, as opposed to the fast and short acting bolus insulins. Insulin degludec is a modified insulin that has one single amino acid deleted in comparison to human insulin, and is conjugated to hexadecanedioic acid via gamma-L-glutamyl spacer at the amino acid lysine at position B29. A significant side effect of insulin therapy is hypoglycemia. A meta-analysis of clinical trials published in July 2012 found 39 to 47.9 events of hypoglycemia (defined as blood glucose ...

Objectives: We aimed to determine the effect of short-term intensive insulin therapy (SIIT) on long-term glycemic control in newly-diagnosed Type-2 diabetes mellitus (nT2DM) patients.. Methods: In this retrospectively study conducted at Sakarya University Medical Faculty Training and Research Hospital Outpatient Clinic between 2016 and 2019, 65 nT2DM patients were enrolled soon after their SIIT was initiated and were followed for at least a year. Intensive insulin treatment was discontinued after three or 12 months in a total of 65 (23-73-year-old) patients who had been newly diagnosed with T2DM. Intensive insulin therapy was discontinued when glycemic control and the target Glycated Hemoglobin (HbA1c) level had been attained, after which oral anti-diabetic drug (OAD), long-term insulin, and diet therapies were pursued.. Results: There was a significant decrease in mean HbA1c from 11.25±1.96% to 6.67±1.07%. Fasting plasma glucose (FPG) was found to be an independent predictor of whether ...

Insulin secretion and glucose disappearance rate were measured in 66 subjects with a wide range of fasting plasma glucose levels. The acute insulin response was present in subjects with fasting glucose levels below 115 mg/dl but was absent above this level. The glucose disappearance rate related to …

Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and

A critical feature of obesity is enhanced insulin secretion from pancreatic beta-cells, enabling the majority of individuals to maintain glycaemic control despite adiposity and insulin resistance. Surprisingly, the factors coordinating this adaptive beta-cell response with adiposity have not been delineated. Here we show that fatty acid binding protein 4 (FABP4/aP2) is an adipokine released from adipocytes under obesogenic conditions, such as hypoxia, to augment insulin secretion. The insulinotropic action of FABP4 was identified using an in vitro system that recapitulates adipocyte to beta-cell endocrine signalling, with glucose-stimulated insulin secretion (GSIS) as a functional readout, coupled with quantitative proteomics. Exogenous FABP4 potentiated GSIS in vitro and in vivo, and circulating FABP4 levels correlated with GSIS in humans. Insulin inhibited FABP4 release from adipocytes in vitro, in mice and in humans, consistent with feedback regulation. These data suggest that FABP4 and insulin form

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 Lancet. Insulin pumps are significantly more effective at controlling blood glucose (sugar) in people with type 2 diabetes who have failed to respond to the usual standard of care, multiple daily insulin injections, according to the largest international study to examine the safety and effectiveness of the pumps to treat type 2 diabetes, published in The Lancet.. Type 2 diabetes is usually controlled by diet and medication, but most people with advanced disease also end up needing insulin therapy to achieve control of their blood sugar. However, roughly a third of these patients struggle to achieve the right level of blood sugar control with insulin injections many times a day. The growing obesity epidemic is adding to the problem by leading to greater insulin resistance.. Insulin pumps are portable devices attached to the body which deliver constant amounts of rapid or short acting insulin via a catheter placed under the skin. Previous randomised trials comparing the efficacy of insulin ...

Insulin secretion from pancreatic beta cells is stimulated by glucose metabolism. However, the relative importance of metabolizing glucose via mitochondrial oxidative phosphorylation versus glycolysis for insulin secretion remains unclear. von Hippel-Lindau (VHL) tumor suppressor protein, pVHL, negatively regulates hypoxia-inducible factor HIF1alpha, a transcription factor implicated in promoting a glycolytic form of metabolism. Here we report a central role for the pVHL-HIF1alpha pathway in the control of beta-cell glucose utilization, insulin secretion, and glucose homeostasis. Conditional inactivation of Vhlh in beta cells promoted a diversion of glucose away from mitochondria into lactate production, causing cells to produce high levels of glycolytically derived ATP and to secrete elevated levels of insulin at low glucose concentrations. Vhlh-deficient mice exhibited diminished glucose-stimulated changes in cytoplasmic Ca(2+) concentration, electrical activity, and insulin secretion, which culminate

The benefit of pre-mixed insulin is that the fast- and long-acting insulin is combined. No mixing of the insulin is necessary, and there is only one injection.. The disadvantage is that NPH, which has a relatively unpredictable action, is the only long-acting insulin that can be used. Also, when the doses in a mixture is increased or decreased, the amount both of the short acting insulin and long-acting insulin changes, which increases the risk of both high and low blood sugars. Mixtures also dont allow a separate correction to be made for high blood sugars.. (You may wonder why there are NO pre-mixed insulins using Lantus and detemir. This is because insulin glargine (Lantus®) and detemir (Levemir®) cannot be mixed in the same syringe with other insulins!). Pre-mixed insulins are usually prescribed for patients needing a simple insulin treatment plan, and sliding scale therapy.. ...

Our previous studies showed that loss-of-function mutation of growth hormone releasing hormone (GHRH) results in increased longevity and enhanced insulin sensitivity in mice. However, the details of improved insulin action and tissue-specific insulin signaling are largely unknown in this healthy-aging mouse model. We conducted hyperinsulinemic-euglycemic clamp to investigate mechanisms underlying enhanced insulin sensitivity in growth hormone (GH) deficient mice. Further, we assessed in vivo tissue-specific insulin activity via activation of PI3K-AKT and MAPK-ERK1/2 cascades using western blot. Clamp results showed that the glucose infusion rate required for maintaining euglycemia was much higher in GHRH-/- mice compared to WT controls. Insulin-mediated glucose production was largely suppressed, whereas glucose uptake in skeletal muscle and brown adipose tissue were significant enhanced in GHRH-/- mice compared to WT controls. Enhanced capacity of insulin-induced activation

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six w …

The initial conclusion here was that metformin only facilitates blood glucose reduction in the presence of insulin. Metformin should, theoretically, blunt the action of insulin. But if we consider that at high levels of insulin the function of that insulin is to limit its own action, I think it would be much better viewed as metformin blunts insulin induced insulin resistance. Insulin was bolused iv at 90 minutes. It will have given a massively supra-physiological plasma level. Insulin induced insulin resistance in the insulin treated group appears to be absent at 30 minutes (ie 120 minutes on the graph), to have started at 60 minutes (150 minutes on the graph) and to have gotten p to below 0.05 at 90 minutes (180 minutes on the graph). Of course under an-insulinaemic conditions there is no insulin signalling to facilitate or block, hence the zero to 90 minutes on the graph where metformin has no effect on blood glucose before insulin was bolused ...

TY - JOUR. T1 - Skeletal muscle insulin resistance. T2 - the interplay of local lipid excess and mitochondrial dysfunction. AU - Chow, Lisa S. AU - From, Arthur H. AU - Seaquist, Elizabeth R. PY - 2010/1. Y1 - 2010/1. N2 - This review explores the complex relationship between excess lipid exposure, mitochondrial dysfunction, and insulin resistance at the level of human skeletal muscle. Lipotoxicity, that is, the elevation of lipids and/or associated lipid metabolites within blood and tissues with subsequent metabolic derangement, has been proposed as a possible mechanism of skeletal muscle insulin resistance. Intravenous lipid infusion is a well-documented method of inducing insulin resistance. Although IMCL content has been correlated with insulin resistance, there is increasing evidence that lipid metabolites such as 4-HNE, DAG, ceramide, and LC-CoA may play a more significant role than TGs in producing skeletal muscle insulin resistance. The association between mitochondrial dysfunction and ...

Visit to know more about the leading player @ Insulin Delivery Device Key Companies and Product Profile. Table of Contents. 1. Key Insights. 2. Executive Summary of Insulin Delivery Device. 3. Insulin Delivery Device: Background and Overview. 3.1. Introduction. 3.2. Types of Insulin Delivery Device. 3.3. Advantages of Insulin Delivery Device. 3.4. Disadvantages of Insulin Delivery Device. 4. Insulin Delivery Device: Regulatory Scenario. 5. Insulin Delivery Device: Reimbursement Scenario. 6. Company Profiles. 6.1 Company Overview. 6.2 Product Portfolio. 6.3 Product description. 6.4 Regulatory Milestones. 6.5 Research and Development. 6.6 Product Development Activities. 7. Insulin Delivery Device Competitive Analysis. 8. KOL Views on Insulin Delivery Device Market. 9. Insulin Delivery Device Market Analysis in 7MM 10. Country-Wise Market size of Insulin Delivery Device. 11. Insulin Delivery Device Market Dynamic (Drivers and Barriers). 12. PEST Analysis. 13. Conclusion and Future ...

AIMS/HYPOTHESIS: The aim of this prospective trial was to compare the effect of different long-acting insulin preparations injected at bedtime on glucose concentrations in patients with type 2 diabetes omitting breakfast and lunch the next day. METHODS: Twenty patients (ten women) with type 2 diabetes who were on an intensified insulin therapy participated. Mean (+/-SD) age was 63 +/- 10 years, diabetes duration 18 +/- 9 years, BMI 32.5 +/- 5 kg/m(2), and HbA(1c) 7.3 +/- 0.7%. Patients received neutral protamine Hagedorn (NPH) insulin, insulin detemir or insulin glargine for at least 2 months; doses were adjusted to achieve morning blood glucose levels of ,7 mmol/l. At the end of the respective treatment period, the long-acting insulin was injected at bedtime (at 22:45 hours) as usual but patients refrained from breakfast and lunch the next day; glucose was measured by a continuous glucose monitoring system (CGMS). RESULTS : Comparable glucose target ranges were reached at midnight (5.8 to 6.1 ...

The type B insulin-resistance syndrome is characterized by the presence of anti-insulin receptor antibodies that cause severe insulin resistance [1, 2]. A 44-year-old, nonobese woman with Hashimoto thyroiditis and the Sjogren syndrome demonstrated severe insulin resistance and acanthosis nigricans. Plasma glucose and insulin levels during oral glucose tolerance testing were 7.3 to 22.1 mmol/L and 4264 to 10 986 pmol/L, respectively. Anti-insulin receptor antibodies were detected in serum, but results of tests for anti-insulin antibody were negative. When oral prednisolone was administered at a starting dose of 40 mg, severe hyperglycemia immediately developed. Because massive insulin ...

The aim of the present thesis was to further increase our understanding of mechanisms contributing to and maintaining cellular insulin resistance in type 2 diabetes (T2D). For this reason, the effects of high glucose and insulin levels on glucose transport capacity and insulin signaling, with emphasis on insulin receptor substrate 1 (IRS-1) were assessed in fat cells. Altered levels of IRS-1 have previously been observed in adipose tissue from insulin-resistant and T2D subjects.. A high glucose level (≥15 mM) for 24 h exerted only a minor impairment on glucose transport capacity in human adipocytes, as opposed to rat adipocytes. However, when combined with a high insulin level (104 µU/ml), basal and insulin-stimulated glucose transport was significantly impaired in both human and rat adipocytes. This was associated with a depletion of IRS-1 and IRS-2 protein levels in rat adipocytes, as a result of post-translational changes and altered gene transcription, respectively. In human adipocytes ...

You searched for: Journal Analytical biochemistry Remove constraint Journal: Analytical biochemistry Publication Year 2012 Remove constraint Publication Year: 2012 Subject noninsulin-dependent diabetes mellitus Remove constraint Subject: noninsulin-dependent diabetes mellitus ...

Title: Biphasic (Premix) Insulin Analogs in Type 2 Diabetes Mellitus. VOLUME: 2 ISSUE: 2. Author(s):Abbas A. Mansour. Affiliation:Department of Medicine, Basrah College of Medicine. Hattin post office. P.O Box: 142 Basrah - 42002, Iraq.. Keywords:Type 2 diabetes mellitus, insulin analogs, glycaemic control. Abstract: One of the causes of failure to achieve target HbA1C in type 2 diabetes mellitus is delay in starting insulin .The standard insulin fails in large number because soluble insulin used for postprandial glucose control does not have a fast enough onset of action ; it needs to be given 30 and 45 minutes before meals ,and has an inappropriately prolonged duration of action, while the longer-acting zinc formulations do not have the long duration of action required of a basal insulin , even with biphasic human insulin. Biphasic insulin analogs allows delivery of both basal and prandial insulin in 1 injection that can be administered closer to mealtime, and produce greater reductions in the ...

SUMMARY. Abnormal glucose tolerance tests and blunted plasma insulin responses returned to normal in three patients and improved in a fourth after removal of a pheochromocytoma. In two subjects phentolamine restored intravenous glucose tolerance curves to normal and improved the insulin secretion response to glucose. These findings suggest that alpha-receptor stimulation by catecholamines is important in causing glucose intolerance and blunted insulin secretion in patients with pheochromocytoma. Tumor removal was more effective than phentolamine in restoring plasma glucose and insulin levels to normal after glucose administration, suggesting that the inhibitory effects of phenochromocytoma on insulin secretion may not be mediated entirely through catecholamine stimulation of alpha-adrenergic receptors. ...

TY - JOUR. T1 - Insulin inhibition of glucose-6-phosphatase gene expression is dependent on the phosphatidylinositol-3-kinase(pi-3-k) pathway, not the ras/map kinase pathway. AU - Baik, S. H.. AU - Trinh, K.. AU - Garcia, I.. AU - Nguyen, K.. AU - Kurland, I. J.. PY - 1997/12/1. Y1 - 1997/12/1. N2 - Glucose-6-phosphatase(G6Pase) is a key enzyme of hepatic gluconeogenesis. The expression of this gene is well known to be inhibited by insulin. but the pathway by which insulin influences this inhibition is not known. Insulin activates a signahng cascade involving the stimulation of insulin receptor tyrosine kinase activity, tyrosine phosphorylation of insulin receptor substrates(IRS-1/2), RasRaf-+p42/p44 Mitogen activated protein(MAP) kinase kinase(MEK)p42/p44 MAP kinase. The sociation of the p85 subunit of PI-3-K with IRS-1/2 confers an increase in the activity of the pl].0 catalytic subunit of PI-3-K which activates Akt/Rac and p70 6 kinase (pT0 S6K). The aim of this study was to evaluate the ...

Central insulin resistance is common to both Type 2 Diabetes and Obesity. Magnetic resonance imaging (MRI) studies that investigated the effects of intranasally administered insulin, have highlighted the involvement of insulin in homeostatic, hedonic and to a lesser extent cognitive regulation of appetite control. This thesis documents a study that set out to explore the effects of intranasal insulin on brain function, using a pharmacological MRI protocol that probed the effects of insulin on resting state connectivity, resting state cerebral perfusion and the cerebral reward response to a food administration paradigm. This study was conducted in a group of healthy, male individuals, with normal and overweight participants. A drug delivery device optimised for efficient nasal delivery of insulin, was employed. A customised, long-label pseudo continuous arterial spin labelling sequence was employed. It was shown that intranasal insulin leads to decreases in cerebral blood flow in the left insula, ...

NPH (Neutral Protamine Hagedorn) is a longer-acting human insulin that is used to cover blood sugar between meals, and to satisfy your overnight insulin requirement. A fish protein, protamine, has been added to the Regular human insulin to delay its absorption. This long acting insulin is a cloudy suspension that needs to be remixed thoroughly before each injection. Because NPH is a suspension of different sized crystals, it has a very unpredictable absorption rate and action. This results in more frequent low and high blood sugars. The use of NPH has declined with the availability of other long-acting insulin options, specifically, the long-acting insulin analogs, insulin glargine and insulin detemir.. ...

Query 11-04: How does real world use of insulin glargine compare to NPH insulin in terms of effectiveness and safety (and ideally cost-effectiveness) for the management of type 1 diabetes mellitus? What is the comparative effectiveness and safety of sitagliptan and NPH insulin for the management of type 2 diabetes (T2D) not controlled by metformin plus sulfonylurea?. This project was originated with a query by British Columbia Ministry of Health in 2013 and funded for 3 years.. Final analysis using Marketscan for both parts of this query were finalized. With T1DM, we found that initiators of NPH insulin were more likely to switch to another insulin therapy after discontinuation (HR: 1.51; 95% CI 1.27-1.79) when compared to initiators of insulin glargine. The risk of hypoglycemia, DKA, and microvascular complications was not significant different among NPH and glargine initiators. With T2DM analysis, we found that initiators of NPH insulin discontinued earlier and have three times higher risk of ...

TY - JOUR. T1 - Characterization of Exercise and Alcohol Self-Management Behaviors of Type 1 Diabetes Patients on Insulin Pump Therapy. AU - Grando, Maria Adela. AU - Groat, Danielle. AU - Soni, Hiral. AU - Boyle, Mary. AU - Bailey, Marilyn. AU - Thompson, Bithika. AU - Cook, Curtiss B.. PY - 2017/3/1. Y1 - 2017/3/1. N2 - Background: There is a lack of systematic ways to analyze how diabetes patients use their insulin pumps to self-manage blood glucose to compensate for alcohol ingestion and exercise. The objective was to analyze real-life insulin dosing decisions occurring in conjunction with alcohol intake and exercise among patients using insulin pumps. Methods: We recruited adult type 1 diabetes (T1D) patients on insulin pump therapy. Participants were asked to maintain their daily routines, including those related to exercising and consuming alcohol, and keep a 30-day journal on exercise performed and alcohol consumed. Thirty days of insulin pump data were downloaded. Participants actual ...

TY - JOUR. T1 - Self-regulating insulin delivery systems. T2 - I. Synthesis and characterization of glycosylated insulin. AU - Jeong, Seo Young. AU - Kim, Sung Wan. AU - Eenink, Martinus J.D.. AU - Feijen, Jan. PY - 1984. Y1 - 1984. N2 - A design for a self-regulating insulin delivery system based on the competitive binding of glucose and glycosylated insulin to the lectin Concanavalin A is proposed. A differnt approach to diabetes therapy is the attempt to effect a permanent cure of the disease by supplementing the patients defective pancreas with a normally functioning transplant. However, pancreatic transplantation in humans is still in its early stage, and the major problems including rejection of the transplants still remain unsolved. In phas one, eight glycosylated insulin derivatives were synthesized. Maltose was directly coupled to bovine insulin by reductive amination. Succinyl- and giutaryl-glucosamine derivatized insulins were synthesized by a mixed anhydride method using the ...

New research that significantly improves our understanding of how insulin interacts with cells in the human body is published today.. The study could have major implications for the development of treatments for Type I diabetes.. By developing and analysing a range of super active insulins, scientists from the York Structural Biology Laboratory at the University of York have been able to identify common features that point to the likely molecular structure of human insulin when it is active in the body.. The research also offers new insight into how insulin binds to insulin receptors on cells.. The research was conducted with colleagues at the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, and is published in the journal Proceedings of the National Academy of Sciences.. Dr Marek Brzozowski, from the York Structural Biology Laboratory, said: The structures of inactive forms of insulin and the insulin receptor are reasonably well known, but ...

Pump therapy is also known as continuous subcutaneous insulin infusion (CSII) and is an alternative way of giving insulin. A pump is a small device which delivers insulin in small frequent pulses. Rather than taking your usual 4-5 daily injections, insulin from the pump is delivered through a soft cannula which sits just under the skin. This is changed every 2-3 days. Unlike injections when you have your background or long acting insulin (such as Lantus or Levemir) plus rapid acting insulin for food (such as Novorapid or Humalog), pumps only run on rapid acting insulin. The pump is programmed with a background or basal rate, which can be altered every hour to meet your changing insulin needs over the 24 hours. This drips in slowly every few minutes. The pump is also programmed with other information specific to you including you such as your insulin to carbohydrate ratios for your meals and your correction factor.. The pump should be worn at all times however it is recommended to take it ...

Background and aim: Acanthosis nigricans (AN) is characterized by hyperpigmented velvety plaques of body folds and neck. Insulin can have a role in the pathogenesis of this disease and hyperinsulinemia as a consequence of insulin resistance may stimulate the formation of the characteristic plaques of AN. In this study insulin resistance was compared in obese women with and without AN.Materials and Methods: Glucose tolerance test (GTT) and fasting blood insulin were measured in two groups of obese women (BMI|30 kg/m2) with AN (32 cases) and without AN (34 cases) and insulin resistance was determined using HOMA formula.Results: The mean fasting blood insulin in two groups with and without AN were 15.5±8.5 and 12.2±4.1 IU/mL; respectively (P|0.05). The mean of insulin resistance in two groups with and without AN were 3.5±1.9 and 2.6±0.9; respectively (P|0.05). The results of GTT showed that the mean fasting blood sugar was 89.5±12 mg/dl and following using glucose were 144±7 mg/dl after 30 minutes,

TY - JOUR. T1 - Effect of gonadotropin-releasing hormone hypogonadism on insulin action as assessed by hyperglycemic clamp studies in men. AU - Chauhan, Subodhsingh. AU - Collins, Karen. AU - Kruger, Michael. AU - Diamond, Michael P.. PY - 2004/4. Y1 - 2004/4. N2 - Objective To investigate the effects of decreasing androgen levels on insulin action, in view of the relationship between hyperandrogenism and impaired insulin action in women with polycystic ovary syndrome. Design Prospective, clinical study. Setting University hospital. Patient(s) Ten normal healthy men. Intervention(s) Gonadotropin-releasing hormone (GnRH) agonist, 3. 75 mg, administered monthly for 3 months. Main outcome measure(s) Insulin action (M/I ratio). Result(s) The M/I ratio decreased from 0.24 ± 0.04 to 0.17 ± 0.04 after GnRH agonist therapy. Conclusion(s) In normal men, administration of a GnRH analogue was associated with a decrease in both testosterone levels and insulin action.. AB - Objective To investigate the ...

Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM). These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity) after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR), insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to

Abstract: In addition to its primary role in regulating glucose production from the liver, glucagon has many other actions, reflected by the wide tissue distribution of the glucagon receptor (Gcgr). To investigate the role of glucagon in the regulation of insulin secretion and whole body glucose homeostasis in vivo, we generated mice overexpressing the Gcgr specifically on pancreatic β-cells (RIP-Gcgr). In vivo and in vitro insulin secretion in response to glucagon and glucose was increased 1.7- to 3.9-fold in RIP-Gcgr mice compared with controls. Consistent with the observed increase in insulin release in response to glucagon and glucose, the glucose excursion resulting from both a glucagon challenge and intraperitoneal glucose tolerance test (IPGTT) was significantly reduced in RIP-Gcgr mice compared with controls. However, RIP-Gcgr mice display similar glucose responses to an insulin challenge. β-Cell mass and pancreatic insulin content were also increased (20 and 50%, respectively) in ...

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis.

AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children.. METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT.. RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (≤ 30 μU/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in ...

Zhu, Caihong; Schwarz, Petra; Abakumova, Irina; Aguzzi, Adriano (2015). Unaltered prion pathogenesis in a mouse model of high-fat diet-induced insulin resistance. PLoS ONE, 10(12):e0144983. ...

TY - JOUR. T1 - Efficacy of insulin analogs in achieving the hemoglobin A 1c target of AU - Giugliano, Dario. AU - Maiorino, Maria Ida. AU - Bellastella, Giuseppe. AU - Chiodini, Paolo. AU - Ceriello, Antonio. AU - Esposito, Katherine. PY - 2011/2. Y1 - 2011/2. N2 - OBJECTIVE - Insulin analogs are increasingly used in patients with type 2 diabetes. We compared the effect of basal, biphasic, prandial, and basal-bolus insulin regimens with insulin analogs to reach the hemoglobin A 1c (HbA 1c) target of 1c target of 30. RESULTS - We found 16 RCTs,with 20 comparisons and 7,759 patients. A greater proportion of patients achieved the HbA1c goal of ,7% with both biphasic (odds ratio 1.88 [95% CI 1.38-2.55]) and prandial (2.07 [1.16-3.69]) insulin compared with basal insulin; this was associated for biphasic insulin with greater hypoglycemia (event/patient/30 days, mean difference, 0.34 [range 0-0.69]) and weight gain in kg (1.0 kg [0.28-1.73]). Compared with biphasic insulin, the basal-bolus regimen ...

Insulin is used to treat people who have diabetes. Each type of insulin acts over a specific amount of time. The amount of time can be affected by exercise, diet, illness, some medicines, stress, the dose, how you take it, or where you inject it. The table below is a general guide. Your results may be different. Insulin strength is usually U-100 (or 100 units of insulin in one milliliter of fluid). Short-acting (regular) insulin is also available in U-500. This is five times more concentrated than U-100 regular insulin. Long-acting insulin (glargine) is also available in U-300. This is three times more concentrated than U-100 long-acting insulin. Be sure to check the concentration of your insulin so you take the right amount.. Insulin is made by different companies. Make sure you use the same type of insulin consistently. ...

Introduction Many guidelines on type 2 diabetes recommend a glycosylated haemoglobin A1c (HbA1c) level below 7%. HbA1c levels in the blood express glucose or glycaemic control over a longer time period (two to three months). During the course of type 2 diabetes it will get more difficult to reach these levels with lifestyle modification (diet, exercise or both) and oral glucose-lowering agents alone. Finally, a substantial number of people will need insulin therapy for better glycaemic control. Insulin therapy can be initiated as insulin alone, called monotherapy (which means that oral glucose-lowering medication will be stopped) or in combination with oral glucose-lowering agents. In the former case, oral blood glucose-lowering agents can be added at a later stage, if insulin monotherapy fails to achieve a good HbA1c level. Hypoglycaemia and weight gain are the most common and well known side effects of insulin therapy. Adding oral agents to insulin could reduce the required insulin dose and ...

Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen with NDC 0002-8233 is a a human prescription drug product labeled by Eli Lilly And Company. The generic name of Insulin Lispro Protamine And Insulin Lispro Injectable Suspension Mix75/25 Kwikpen is insulin lispro.

TY - JOUR. T1 - Insulin receptor substrate 1 and 2 (IRS1 and IRS2). T2 - What a tangled web we weave. AU - Watersand, Steven B.. AU - Pessin, Jeffrey E.. PY - 1996/1. Y1 - 1996/1. N2 - The insulin receptor is a transmembrane tyrosine kinase that is essential for mediating multiple intracellular signalling cascades that lean ultimately to the biological actions of insulin. Tyrosine phosphorylation of the cytosolic proteins insulin receptor substrate 1 and 2 (IRS1 and IRS2) produces protein scaffolding for the assembly of effector proteins containing Src homology 2 (SH2) domains, thereby generating multisubunit signalling complexes. Although IRS1 was originally isolated as a specific insulin receptor substrate, both IRS1 and IRS2 appear to play a broader role, functioning also as proximal substrates in growth hormone and cytokine receptor signalling. Current data establish IRS1 and IRS2 as critical effecters integrating various cell-type-specific signals into distinct, but overlapping, ...

Author(s): Hivert, Marie-France; Cardenas, Andres; Allard, Catherine; Doyon, Myriam; Powe, Camille E; Catalano, Patrick M; Perron, Patrice; Bouchard, Luigi | Abstract: The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ∼26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where

TNF-α is an inflammatory cytokine that plays an important role in insulin resistance observed in obesity and chronic inflammation. Many cellular components involved in insulin signaling cascade are known to be inhibited by TNF-α. Insulin receptor substrate (IRS)-1 is one of the major targets in TNF-α-induced insulin resistance. The serine phosphorylation of IRS-1 enables the inhibition of insulin signaling. Until now, many studies have been conducted to investigate the mechanism of TNF-α-induced insulin resistance based on Western blot. Intracellular protein kinase crosstalk is commonly encountered in inflammation-associated insulin resistance. The crosstalk among the signaling molecules obscures the precise role of kinases in insulin resistance. We have developed a cell lysis-free quantum dots (QDots) multicolor cellular imaging to identify the biochemical role of multiple kinases (p38, JNK, IKKβ, IRS1ser, IRS1tyr, GSK3β, and FOXO1) in inflammation-associated insulin resistance pathway with a

BackgroundDiabetes is associated with long-term damage, dysfunction and failure of various organs, especially the eyes, kidneys, nerves, heart and blood vessels. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Insulin resistance is a fundamental aspect of the aetiology of type 2 diabetes. Insulin resistance has been shown to be associated with atherosclerosis, dyslipidaemia, glucose intolerance, hyperuricaemia, hypertension and polycystic ovary syndrome. The mineral zinc plays a key role in the synthesis and action of insulin, both physiologically and in diabetes mellitus. Zinc seems to stimulate insulin action and insulin receptor tyrosine kinase activity.ObjectivesTo assess the effects of zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance.Search methodsThis review is an update of a previous Cochrane systematic review published in 2007. We searched the Cochrane Library (2015, Issue 3), MEDLINE, ...

Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities. These cell cultures expressed a variety of muscle-specific phenotypes including the proteins alpha-actinin and myosin, muscle-specific creatine kinase activity, and RNA encoding GLUT4, MYF5, MYOD1, and MYOGENIN. Labeled glucose was used to measure the insulin-stimulated conversion of glucose to glycogen in these cultures. The in vivo rates of insulin-stimulated glycogen production (insulin resistance) were correlated with in vitro measures of glycogen production (P = 0.007, r = 0.58). This defect in insulin action is stable ...

TY - JOUR. T1 - Molecular scanning for mutations in the β3-adrenergic receptor gene in nauruans with obesity and noninsulin-dependent diabetes mellitus. AU - Silver, Kristi. AU - Walston, Jeremy D. AU - Wang, Yihong. AU - Dowse, Gary. AU - Zimmet, Paul. AU - Shuldiner, Alan R.. PY - 1996. Y1 - 1996. N2 - We recently identified a mutation in the human β3-adrenergic receptor (β3AR) gene (codon 64 TGG(Trp)→CGG(Arg); TRP64ARG) that associates with features of the insulin resistance syndrome and an earlier onset of noninsulin-dependent diabetes mellitus (NIDDM). We scanned the β3AR gene for mutations by single stranded conformational polymorphism analysis in 20 Nauruans with obesity and NIDDM. No mutations were identified. Sixty-five Nauruan subjects were genotyped for the TRP64ARG β3AR. All subjects were homozygous for the normal allele. We genotyped Samoans and Asians for the TRP64ARG β3AR. Seven of 52 Samoans were heterozygous for the mutant arginine allele (allele frequency, 0.07). Of ...

View more ,Abstract: Insulin resistance ensues when normal physiological concentrations of insulin are unable to induce effective cellular insulin signalling and glucose uptake by insulin sensitive tissues. It is caused by several abnormalities that include; 1) an overabundance of circulating free fatty acids (and dyslipidaemia), 2) systemic inflammation caused by increased tissue and circulating pro-inflammatory cytokines, and, 3) over activation of the systemic and organ specific renin-angiotensin systems. Although usually associated with obesity, insulin resistance is not a condition that only afflicts obese individuals. Dyslipidaemia which is implicated in the aetiology of insulin resistance can be caused by adipose tissue expansion (obesity) or the increased consumption of lipogenic fructose which has profound effects on liver metabolism and serum lipid profiles. The primary reason fructose is implicated in insulin resistance is because it induces hepatic lipogenesis which would directly ...

Insulin receptor substrates (IRS)-5 and -6 are two recently identified members of the IRS family. We investigated their roles as insulin receptor substrates and compared them with Src-homology-2-containing (Shc) protein, a well-established substrate. Bioluminescence resonance energy transfer (BRET) experiments showed no interaction between the receptor and IRS-5, while interaction with IRS-6 was not enhanced by insulin. By contrast, Shc showed an insulin-induced BRET response, as did a truncated form of IRS-1 (1-262). While Shc was heavily phosphorylated after stimulation of the insulin receptor, IRS-5 and -6 showed very weak phosphorylation levels. These results suggest that, although these two adaptors have previously been proposed as substrates for the insulin receptor, they are poor substrates for the insulin receptor. This calls into question their relevance to insulin signalling.