Central leptin increases peripheral insulin sensitivity through unknown mechanisms. Central insulin signaling may also contribute to peripheral insulin sensitivity. To clarify the relationships among central leptin, central insulin, peripheral insulin sensitivity, and adiponectin, we examined the effects of intracerebroventricular leptin and insulin on peripheral insulin sensitivity and adiponectin concentrations in streptozotocin (STZ)-induced diabetic rats. Rats were cannulated in the lateral ventricle. Intravenous STZ was injected to induce diabetes. After establishment of hyperglycemia in STZ-treated rats, insulin (10 mU/day), leptin (10 µg/day), or vehicle was administered daily for 10 days. After one week of central administration, in vivo insulin sensitivity was measured by injecting IV insulin (0.025 U/kg body weight) and measuring blood glucose concentration 15 minutes after the injection. Rats treated with central leptin had increased peripheral insulin sensitivity. In addition, blood ...

The current insulin therapy is divided into the conventional insulin therapy (1~2 injections per day) and the intensive insulin therapy (3~4 injections per day). The kinetics of exogenous insulin in the intensive insulin therapy imitate the kinetics of insulin secretion in a healthy person. A previous large clinical study (e.g. DCCT, Kumamoto study, etc.) suggested that intensive insulin therapy prevented microangiopathy and macroangiopathy, and inhibited progression of them, however many patients chose conventional insulin therapy because many hoped that they injected insulin as few as possible. The patients thought that their life styles were disturbed by many times of insulin injection.. The current dual-acting insulin made from insulin as part modified by protamine is able to suppress postprandial hyperglycemia. The new insulin may possibly have the kinetics of insulin in the patient who uses insulin as the intensive insulin therapy. Moreover, the patients will receive the insulin therapy ...

TY - JOUR. T1 - Effect of insulin therapy on body fat distribution in NIDDM patients with secondary sulfonylurea failure. T2 - A preliminary report. AU - Takei, I.. AU - Takayama, S.. AU - Yamauchi, A.. AU - Nakamoto, S.. AU - Kitamura, Y.. AU - Katsukawa, Fuminori. AU - Yamazaki, H.. AU - Saruta, T.. AU - Inoue, S.. PY - 1998/2. Y1 - 1998/2. N2 - Objective: To clarify the influence of insulin therapy on body weight and fat distribution, we compared these parameters in five non-insulin dependent diabetes mellitus (NIDDM) patients, with secondary sulfonylurea failure, before and after insulin therapy. Body weight increased significantly after instituting insulin treatment. However, the visceral to subcutaneous fat (V/S) ratio decreased significantly due to a marked increase in S-fat without a change in V-fat. Insulin therapy necessitated by sulfonylurea failure does not appear to accelerate the atherogenic process in NIDDM patients as there is no increase in visceral fat.. AB - Objective: To ...

TY - JOUR. T1 - Exendin-4 as a stimulator of rat insulin I gene promoter activity via bZIP/CRE interactions sensitive to serine/threonine protein kinase inhibitor Ro 31-8220. AU - Chepurny, Oleg G.. AU - Hussain, Mehboob A.. AU - Holz, George G.. PY - 2002. Y1 - 2002. N2 - Signal transduction properties of exendin-4 (Ex-4) underlying its ability to stimulate rat insulin I gene promoter (RIP1) activity were assessed in the pancreatic β-cell line INS-1. Ex-4 acted via glucagon-like peptide-1 receptors to stimulate RIP1 in a glucose-dependent manner, as measured in cells transfected with a -410-bp RIP1-luciferase construct (RIP1-Luc). The action of Ex-4 was independent of cAMP and PKA because it was not blocked by cotransfection with dominant-negative Gαs, was unaffected by pretreatment with the membrane-permeant cAMP antagonist 8-Br-Rp-cAMPS, and remained apparent after treatment with PKA inhibitors H-89 or KT 5720. Similarly, cotransfection with a dominant-negative isoform of the type-2 ...

TY - JOUR. T1 - Glucose-stimulated insulin secretion is coupled to the interaction of actin with the t-SNARE (target membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein) complex. AU - Thurmond, Debbie C.. AU - Gonelle-Gispert, Carmen. AU - Furukawa, Megumi. AU - Halban, Philippe A.. AU - Pessin, Jeffrey E.. PY - 2003/4/1. Y1 - 2003/4/1. N2 - The actin monomer sequestering agent latrunculin B depolymerized β-cell cortical actin, which resulted in increased glucose-stimulated insulin secretion in both cultured MIN6 β-cells and isolated rat islet cells. In perifused islets, latrunculin B treatment increased both first- and second-phase glucose-stimulated insulin secretion without any significant effect on total insulin content. This increase in secretion was independent of calcium regulation because latrunculin B also potentiated calcium-stimulated insulin secretion in permeabilized MIN6 cells. Confocal immunofluorescent microscopy revealed a redistribution of ...

The Insulin Index of a food represents how much it elevates the concentration of insulin in the blood during the two-hour period after the food is ingested. The index is similar to the Glycemic Index (GI) and Glycemic Load (GL), but rather than relying on blood glucose levels, the Insulin Index is based upon blood insulin levels. The Insulin Index represents a comparison of food portions with equal overall caloric content (250 kcal or 1000 kJ), while GI represents a comparison of portions with equal digestible carbohydrate content (typically 50 g) and the GL represents portions of a typical serving size for various foods. The Insulin Index can be more useful than either the Glycemic Index or the Glycemic Load because certain foods (e.g., lean meats and proteins) cause an insulin response despite there being no carbohydrates present, and some foods cause a disproportionate insulin response relative to their carbohydrate load. Holt et al. have noted that the glucose and insulin scores of most ...

In our updated meta-analysis of randomized trials of intensive insulin therapy in critically ill patients, we found that such therapy had no effect on the overall risk of death. By including data from the largest trial of intensive insulin therapy, which was recently published,18 we provide the most current and precise estimate of the effect of intensive insulin therapy on mortality and severe hypoglycemia in the ICU setting. We found significant heterogeneity between studies, which was driven primarily by the 2 trials involving surgical patient populations.8,29 In keeping with this observation, our meta-regression analysis suggested that intensive insulin therapy may benefit patients in surgical ICUs. Finally, there was a 6-fold increased risk of severe hypoglycemia among patients given intensive insulin therapy compared with the control treatment. The risk of hypoglycemic events did not differ by type of ICU, or by intensity of insulin therapy.. Our meta-analysis showed a similar overall ...

Tenders from Ukraine for insulin human insulin human insulin human insulin human insulin human insulin human insulin glulisine insulin glargin insulin glargin insulin human insulin human insulin human insulin human insulin hu.... EuropeThe tender reference number is 19395499 and it is closing on 26th Jan 2019.

TY - JOUR. T1 - Insulin enhances glucose-stimulated insulin secretion in healthy humans. AU - Bouche, Clara. AU - Lopez, Ximena. AU - Fleischman, Amy. AU - Cypess, Aaron M.. AU - OShea, Sheila. AU - Stefanovski, Darko. AU - Bergman, Richard N.. AU - Rogatsky, Eduard. AU - Stein, Daniel T.. AU - Kahn, C. Ronald. AU - Kulkarni, Rohit N.. AU - Goldfine, Allison B.. PY - 2010/3/9. Y1 - 2010/3/9. N2 - Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) clamps using B28-Asp insulin that could be immunologically distinguished from endogenous insulin. Insulin and ...

Basal insulin therapy is used by people with both type 1 and type 2 diabetes. Glucose is continuously released by the liver throughout the day when there is no food being digested. There are different ways that different types of insulin can mimic the action of this basal insulin in the body.. For people with type 1 and 2 diabetes, long-acting insulin is injected once or twice a day to mimic basal insulin. Those with type 1 would then take insulin to cover mealtimes. Mealtime treatment for type 2 diabetes varies.. For those with type 1 diabetes who are on a pump, quick-acting insulin is delivered at a low rate continuously throughout the day and night, and then a bolus amount of insulin is given to cover meals. Using the insulin pump is a good way to adjust the basal insulin levels in a very precise manner. You can program the basal insulin output such that it can match the bodys normal insulin production.. One study looked into the efficacy of basal insulin in being able to improve the A1c ...

We investigated the mechanisms by which peripheral or portal insulin can independently alter liver glucose production. Isotopic ([3-3H]glucose) and arteriovenous difference methods were used in conscious overnight-fasted dogs. A pancreatic clamp (somatostatin plus basal insulin and basal glucagon infusions) was used to control the endocrine pancreas. After a 40-min basal period, a 180-min experimental period followed in which selective increases in peripheral (PERI group, n = 5) or portal-vein (PORT group, n = 5) insulin were induced. In control dogs (CONT group, n = 10), insulin was not increased. Glucagon levels were fixed in all studies, and basal euglycemia was maintained by peripheral glucose infusion in the two experimental groups. In the PERI group, arterial insulin rose from 36 ± 12 to 120 ± 12 pmol/l, while portal insulin was unaltered. In the PORT group, portal insulin rose from 108 ± 42 to 192 ± 42 pmol/l, while arterial insulin was unaltered. Neither arterial nor portal insulin ...

The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patients breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be

The need for the delivery of insulin by injection can be reduced or eliminated by delivering an aerosolized monomeric insulin formulation. Repeatability of dosing and more particularly the repeatability of the blood concentration versus time profile is improved relative to regular insulin. The blood concentration versus time profile is substantially unaffected by specific aspects of the patients breathing maneuver at delivery. Further, the rate at which blood glucose is lowered is increased by the use of monomeric insulin. Particles of insulin and in particular monomeric insulin delivered to the surface of lung tissue will be absorbed into the circulatory system. The monomeric insulin may be a dry powder but is preferably in a liquid formulation delivered to the patient from a hand-held, self-contained device which automatically releases an aerosolized burst of formulation. The device includes a sensor which is preferably electronic which measures inspiratory flow and volume which measurement can be

Numerous prospective studies in various populations indicate that insulin resistance and insulin secretory dysfunction predict the development of type 2 diabetes (1,2,3,4,5,6). However, the majority of these studies included both individuals with NGT and IGT at baseline and used indirect measures of insulin action and insulin secretion derived from an OGTT. Moreover, to date, only two groups of investigators have examined the metabolic predictors of progression from NGT to IGT (6,8). Thus, although these studies provide evidence for a pathogenic role of insulin resistance and insulin secretory dysfunction in the development of type 2 diabetes, they give only limited information as to the relative importance of these abnormalities during the different stages of the development of the disease.. In the present study, we addressed this question by assessing the predictive effects of insulin resistance and low early-phase insulin secretion separately for the progression from NGT to IGT and also from ...

The current study represents a further contribution to the search of molecular transducers involved in the insulin-sensitizing effect of exercise. Here, we provide evidence to support that AMPK is necessary for increasing insulin sensitivity to stimulate glucose uptake in EDL muscle after in situ contraction, as well as enhancing whole-body insulin sensitivity and insulin-stimulated muscle glucose uptake after a single bout of acute exercise. We establish a causal link between a contraction-regulated signal and the subsequent improvement in muscle insulin sensitivity. On the basis of our findings, we propose that contraction-induced activation of AMPK potentiates the ability of insulin to increase phosphorylation of TBC1D4 leading to enhanced muscle glucose uptake.. Theoretically, synthesis of new proteins involved in muscle glucose uptake may mediate improvements in skeletal muscle insulin sensitivity after contraction. However, we found that greater insulin-stimulated glucose uptake after ...

This dissertation work is focused on the insulin-signal-transduction pathways to glucose transport in skeletal muscle from animal models of NIDDM. The overall objective is to determine the effectiveness of different pharmacological treatments to improve insulin action in skeletal muscle. Muscle-fiber-type-specific differences in insulin signal transduction was first considered. We noted increased insulin action on insulin signaling events including; IR, IRS- 1, IRS-2, PI 3-kinase, and AKT occur in oxidative soleus muscle versus glycolytic EPI and EDL muscles. The time course for insulin signal transduction was similar between oxidative and glycolytic muscles. We assessed the molecular mechanism underlining insulin resistance in skeletal muscle from diabetic the Goto- Kakizaki (GK) rats, a non-obese model of NIDDM. Impaired insulin signaling and glucose transport occurred in a muscle-fiber-type specific manner in GK rats. For glucose transport, defects in maximal insulin stimulation occurred in ...

TY - JOUR. T1 - Autocrine effect of Zn2+ on the glucose-stimulated insulin secretion. AU - Slepchenko, Kira G.. AU - Daniels, Nigel A.. AU - Aili, Guo. AU - Li, Yang V.. PY - 2015/9/25. Y1 - 2015/9/25. N2 - It is well known that zinc (Zn2+) is required for the process of insulin biosynthesis and the maturation of insulin secretory granules in pancreatic beta (β)-cells, and that changes in Zn2+ levels in the pancreas have been found to be associated with diabetes. Glucose-stimulation causes a rapid co-secretion of Zn2+ and insulin with similar kinetics. However, we do not know whether Zn2+ regulates insulin availability and secretion. Here we investigated the effect of Zn2+ on glucose-stimulated insulin secretion (GSIS) in isolated mouse pancreatic islets. Whereas Zn2+ alone (control) had no effect on the basal secretion of insulin, it significantly inhibited GSIS. The application of CaEDTA, by removing the secreted Zn2+ from the extracellular milieu of the islets, resulted in significantly ...

TY - JOUR. T1 - A new technique to assess insulin sensitivity in humans. T2 - The Rapid Insulin Sensitivity Test (RIST). AU - Patarrão, Rita S.. AU - Wayne Lautt, W.. AU - Guarino, Maria P.. AU - Afonso, Ricardo A.. AU - Ribeiro, Rogério T.. AU - Fernandes, Ana B.. AU - Boavida, José M.. AU - Macedo, Maria Paula. PY - 2007/12/1. Y1 - 2007/12/1. N2 - The objective of this study was to develop a Rapid Insulin Sensitivity Test (RIST) in humans, a test already used in animal studies. Insulin sensitivity was assessed using a rapid modified euglycemic clamp, the RIST. In this test, glucose disposition was determined after an intravenous (IV) bolus (50mU/kg bw administered over 30 seconds) of insulin, before and after feeding a standardized test meal, in healthy male subjects (aged 27.8±2.4 years, BMI 23.5±1.2 kg/m2). The RIST uses as the index of insulin sensitivity, the total amount of glucose required to be infused to maintain euglycemia during insulin action following an IV bolus of insulin. ...

The pancreatic beta cell is an incredible machine producing tens of thousands of insulin molecules every second. When this process works normally, the result is tight regulation of blood glucose and whole body energy stores. However, breakdowns in insulin processing can rapidly overwhelm the beta cell leading to beta cell stress, destruction, and ultimately diabetes. A striking example of this breakdown can be found in the disease MIDY (Mutant INS-gene induced Diabetes of Youth) in which production of a single mutant insulin molecule leads to dominant beta cell failure and diabetes. Now, Cunningham et al. report a potential new pathway that can be exploited to diminish mutant insulin and restore normal insulin secretion.. Misfolded proteins are commonly trapped in the endoplasmic reticulum (ER) where they are triaged by a process known as ER-associated degradation (ERAD) and ultimately destroyed by the cytoplasmic proteasome. Unfortunately, due to insulins capacity to form disulfide bonds, ...

Small and speedy. Human insulin is a hormone that is produced in the pancreas and secreted to aid in the bodys uptake of glucose. The insulin molecule consists of an A region and a B region. Diabetes mellitus disorders arise from impairment of the bodys normal production of insulin. The most effective treatment for diabetes is injection of synthetic insulin.. But a part of the B region causes insulin molecules to stick together and form aggregations of six insulin molecules. Its how insulin is stored in the pancreas. But injected insulin must de-aggregate into individual molecules before doing a person any good - and that process can take up to an hour. The fastest-acting insulin on the market, Humalog, still takes 15-30 minutes to become active. The ideal scenario would be to take the region off of the B chain Safavi says. But then you completely abolish insulin activity.. Chou, Safavi, and colleagues found that insulin produced by the cone snail Conus geographus lacked the segment ...

What is Insulin Resistance?. Under normal circumstances, insulin is tightly controlled by a natural homoeostatic feedback mechanism. With every meal, insulin is released as carbohydrates enter the blood stream. In a healthy body, the insulin receptors in the cell membranes respond to the hormone, and take up carbohydrates and other nutrients. This, in turn, reduces the production of insulin.. The problem starts when the tissue fails to respond to insulin. When this happens, the sugar in the blood remains high despite the presence of insulin, and the body has no choice but to release more insulin. It becomes a vicious cycle because it is actually the presence of insulin that makes the tissue more and more resistant to it.. This is how insulin exposure determines the rate of ageing: with every insulin release, cell membranes become a little bit more insulin resistant. A gradual increase in insulin concentration over time is normal, but the current epidemic of severe insulin resistance is a modern ...

The second messenger cAMP mediates potentiation of glucose-stimulated insulin release. Use of inhibitors of cAMP-hydrolyzing phosphodiesterase (PDE) 3 and overexpression of PDE3B in vitro have demonstrated a regulatory role for this enzyme in insulin secretion. In this work, the physiological significance of PDE3B-mediated degradation of cAMP for the regulation of insulin secretion in vivo and glucose homeostasis was investigated in transgenic mice overexpressing PDE3B in pancreatic beta-cells. A 2-fold overexpression of PDE3B protein and activity blunted the insulin response to intravenous glucose, resulting in reduced glucose disposal. The effects were dose-dependent because mice overexpressing PDE3B 7-fold failed to increase insulin in response to glucose and hence exhibited pronounced glucose intolerance. Also, the insulin secretory response to intravenous glucagon-like peptide 1 was reduced in vivo. Similarly, islets stimulated in vitro exhibited reduced insulin secretory capacity in ...

A system and method for generating a personalized diabetes management tool for diabetes mellitus is provided. An insulin activity curve for a patient population for an insulin preparation for diabetes mellitus treatment is identified. A personal insulin activity model for the patient is generated. An insulin sensitivity is determined by taking a derivative of the rate of change of blood glucose over time for the insulin preparation. An insulin sensitivity coefficient for the insulin preparation for a patient of diabetes mellitus is established. The insulin sensitivity coefficient is applied to the patient population insulin activity curve over a duration of action of the insulin preparation.

Intensive insulin therapy or flexible insulin therapy is a therapeutic regimen for diabetes mellitus treatment. This newer approach contrasts with conventional insulinotherapy. Rather than minimize the number of insulin injections per day (a technique which demands a rigid schedule for food and activities), the intensive approach favors flexible meal times with variable carbohydrate as well as flexible physical activities. The trade-off is the increase from 2 or 3 injections per day to 4 or more injections per day, which was considered intensive relative to the older approach. In North America in 2004, many endocrinologists prefer the term flexible insulin therapy (FIT) to intensive therapy and use it to refer to any method of replacing insulin that attempts to mimic the pattern of small continuous basal insulin secretion of a working pancreas combined with larger insulin secretions at mealtimes. The semantic distinction reflects changing treatment. Long-term studies like the UK ...

Podcast: Play in new window , Download. Subscribe: Apple Podcasts , Android , RSS. In episode 99 of the Real World Wellness podcast, Christine explains the critical role that insulin plays in lowering your glucose levels and how problems occur with insulin and lead to insulin resistance before you can detect prediabetes and type 2 diabetes. Since insulin resistance is associated with metabolic syndrome, PCOS, cancer, diabetes, and many other diseases, you want to get your insulin levels tested. Christine explains the risk factors for insulin resistance and what test to ask for. She also talks about the insulin index for food and beverages and what healthy foods produce a high insulin response and should be avoided.. Resources:. https://www.ncbi.nlm.nih.gov/pubmed/18936729. https://www.ncbi.nlm.nih.gov/pubmed/17259468. https://www.ncbi.nlm.nih.gov/pubmed/18096375?log$=activity. Next Episode: Christine will talk more about strategies to increase insulin sensitivity ranging from supplements to ...

Elevated non-esterified fatty acid (NEFA) levels may influence insulin secretion and contribute to the development of Type 2 DM. We investigated the effects of acute NEFA elevation in controls (n = 6) and subjects predisposed to Type 2 DM (n = 6) on basal insulin levels, and following glucose and arginine stimulation. Each subject had one study with a triglyceride (TG) plus heparin infusion (elevated NEFA levels) and another with normal saline. Twenty minutes after the TG or saline infusion began a glucose bolus was given and 10 min later a 90-min hyperglycaemic clamp (approximately 9 mmol l(-1)) was started. Intravenous arginine was given at 110 min. Elevated NEFA levels (approximately 4000 micromol l(-1)) did not enhance basal or first phase glucose stimulated insulin levels. During hyperglycaemia, NEFA elevation further increased insulin levels in both groups by 20-44% (p | 0.05) and C-peptide levels by 17-25% (p | 0.05). The post-arginine insulin levels during hyperglycaemia were increased by 45% in

589. An individual may get diabetes when the pancreas can no longer secrete the needed hormones that produce insulin. The insulin maintains the glucose in the blood to be normal. Low insulin means that the level of glucose, which is sugar in the blood, may get high and may lead to diabetes.. The autoimmune reaction is a type 1 diabetes where the cells in the pancreas organ that produces the needed insulin are destroyed. This results to the total loss of insulin in the hormones. …. diabetes. An individual may get diabetes when the pancreas can no longer secrete the needed hormones that produce insulin. The insulin maintains the glucose in the blood to be normal. Low insulin means that the level of glucose, which is sugar in the blood, may get high and may lead to diabetes.. The autoimmune reaction is a type 1 diabetes where the cells in the pancreas organ that produces the needed insulin are destroyed. This results to the total loss of insulin in the hormones. This happens because the body has ...

The importance of non-glucose carbohydrates, especially mannose and inositol, for normal development is increasingly recognized. Whether pregnancies complicated by abnormal glucose transfer to the fetus also affect the regulation of non-glucose carbohydrates is unknown. In pregnant sheep, maternal insulin infusions were used to reduce glucose supply to the fetus for both short (2-wk) and long (8-wk) durations to test the hypothesis that a maternal insulin infusion would suppress fetal mannose and inositol concentrations. We also used direct fetal insulin infusions (1-wk hyperinsulinemic-isoglycemic clamp) to determine the relative importance of fetal glucose and insulin for regulating non-glucose carbohydrates. A maternal insulin infusion resulted in lower maternal (50%, P | 0.01) and fetal (35-45%, P | 0.01) mannose concentrations, which were highly correlated (r2 = 0.69, P | 0.01). A fetal insulin infusion resulted in a 50% reduction of fetal mannose (P | 0.05). Neither maternal nor fetal plasma

Abstract:. Diabetes mellitus is a disease characterized by poor glycemic control which often leads to severe complications including cardiovascular disease and kidney failure. Many diabetic patients continually monitor their blood sugar and self-administer multiple daily doses of exogenous insulin to combat hyperglycemia. To reduce this patient burden, limit the occurrence of hypoglycemic events, and better mimic native insulin activity, therapies which can self-regulate insulin delivery are an attractive option. In this lecture, Volpatti will discuss three different glucose-responsive insulin delivery systems that she developed during her Ph.D. toward achieving this goal. These polymeric delivery systems encapsulate and store insulin until it is needed to combat elevated blood sugar levels. In normal glucose conditions, insulin release is minimal but is rapidly (, 1 h) released in response to hyperglycemia in a diabetic mouse model. More generally, the platforms developed here may be used for ...

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. Approximately 95% of patients with Type 1 diabetes develop some degree of retinopathy within 25 years of diagnosis despite normalization of blood glucose by insulin therapy. The goal of this study was to identify molecular changes in the rodent retina induced by diabetes that are not normalized by insulin replacement and restoration of euglycemia. The retina transcriptome (22,523 genes and transcript variants) was examined after three months of streptozotocin-induced diabetes in male Sprague Dawley rats with and without insulin replacement for the later one and a half months of diabetes. Selected gene expression changes were confirmed by qPCR, and also examined in independent control and diabetic rats at a one month time-point. Transcriptomic alterations in response to diabetes (1376 probes) were clustered according to insulin responsiveness. More than half (57%) of diabetes-induced mRNA changes (789 probes) observed at

IGFs are important regulators of pancreatic beta-cell development, growth, and maintenance. Mutations in the IGF genes have been found to be associated with type 2 diabetes, myocardial infarction, birth weight, and obesity. These associations could result from changes in insulin secretion. We have analyzed glucose-stimulated insulin secretion using hyperglycemic clamps in carriers of a CA repeat in the IGF-I promoter and an ApaI polymorphism in the IGF-II gene. Normal and impaired glucose-tolerant subjects (n = 237) were independently recruited from three different populations in the Netherlands and Germany to allow independent replication of associations. Both first- and second-phase insulin secretion were not significantly different between the various IGF-I or IGF-II genotypes. Remarkably, noncarriers of the IGF-I CA repeat allele had both a reduced insulin sensitivity index (ISI) and disposition index (DI), suggesting an altered balance between insulin secretion and insulin action. Other diabetes

There is a recognised need to develop insulin products with faster onset of action compared with the current state-of-the-art prandial insulin products. Prandial insulin is used by diabetics to control the blood glucose rise after meals. To ensure effective blood glucose management it is essential that, once injected, insulin begins to act as rapidly as possible. Whilst there has been good progress in developing rapid acting insulins in the last two decades, there is a strong need to develop products that are even more rapid-acting to ensure lower variability of post-meal blood glucose elevations and lower rates of hypoglycaemia. Ultra-rapid acting insulin is also a key component required for the development of efficient closed-loop pump systems that would enable automatic glucose control based on a combination of continuous glucose measurement, smart algorithms to decide how much insulin ultra-rapid acting insulin to deliver via an insulin pump. The rapidity of response is critical in such ...

Insulin was the first hormone measured successfully by radioisotope immunoassay, and insulin assay is now available in most sizable reference laboratories. Insulin is excreted primarily through the kidneys. In general, juvenile diabetics have low fasting insulin levels, and an OGTT using insulin determinations usually produces a flat curve. Mild diabetics have normal fasting insulin levels and display an insulin GTT curve that has a delayed rise, either to normal height or to a point moderately above normal; in either case the curve thereafter falls in a normal fashion. Decreased tolerance due to many other causes produces similar curves; an insulin OGTT has not been more efficient in uncovering subclinical diabetes than blood glucose OGTT. Some maintain that the ratio of insulin values to glucose values obtained on the same specimen during the OGTT is more reliable than insulin values alone. At any rate, most investigators believe that, at present, plasma insulin levels should not be used for ...

TY - JOUR. T1 - Lack of change of lipoprotein(a) levels by the optimization of glycemic control with insulin therapy in NIDDM patients. AU - Caixas̀, Assumpta. AU - Pérez, Antonio. AU - Ordóñez-Llanos, Jordi. AU - Bonet, Rosa. AU - Rigla, Mercedes. AU - Castellví, Agustina. AU - Bayén, L.. AU - De Leiva, Alberto. PY - 1997/1/1. Y1 - 1997/1/1. N2 - OBJECTIVE - To evaluate the effect of glycemic control improvement with insulin therapy on lipoprotein(a) [Lp(a)] levels in patients with NIDDM. RESEARCH DESIGN AND METHODS - We performed a longitudinal study in a tertiary referral center to compare lipid and Lp(a) levels before and after 3 months of insulin therapy in 60 poorly controlled NIDDM patients (32 men, 28 women). Patients previously treated with oral hypoglycemic agents (n = 50) received one to two insulin doses, and those previously treated with insulin (n = 10) received multiple insulin doses. Lp(a) levels were measured by the Terumo method. Differences between the two periods were ...

Obesity is considered a state of low-grade inflammation, and this inflammation is strongly related to development of systematic insulin resistance. Hyperglycemia develops during insulin resistance as insulin-stimulated glucose uptake in peripheral insulin sensitive tissues is reduced. Hepatic insulin resistance is often accompanied with increased gluconeogenesis and increased hepatic glucose output, which further increase blood glucose. To cope with the hyperglycemia, the pancreatic -cells compensate by increasing insulin secretion. However, after a certain amount of time, the -cells are no longer able to compensate, and insulin production stops. This may be accompanied with apoptosis in the -cells. Indomethacin is an NSAID and a non-selective inhibitor of cyclooxygenase 1 (COX-1) and 2 (COX-2). In this study we have demonstrated that COX-inhibition using indomethacin, attenuated high fat/high sucrose-induced obesity in C57BL/6J mice. Obesity and glucose intolerance ...

The risk of surgical site infection has been reported to be higher in patients with poorly controlled diabetes. Since chronic hyperglycemia impairs neutrophil functions, preoperative glycemic control may restore neutrophil function. However, long-term insulin therapy may lead to a delay in surgery, which may be a problem, especially in cancer surgery. It is therefore unfortunate that there have been few studies in which the optimal duration of perioperative glycemic control for diabetes with chronic hyperglycemia was investigated. Therefore, we investigated the effects of preoperative long-term insulin therapy and short-term insulin therapy on perioperative neutrophil functions in diabetic mice with chronic hyperglycemia. Five-week-old male C57BL/6 J mice were divided into four groups (No insulin (Diabetes Mellitus: DM), Short-term insulin (DM), Long-term insulin (DM), and Non-diabetic groups). Diabetes was established by administrating repeated low-dose streptozotocin. The Short-term insulin (DM) group

β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn2+-free insulin but strongly affects RIA measurements of Zn2+-insulin. In contrast, accurate determination of Zn2+-insulin was obtained only when bovine serum albumin or Zn2+ ...

TY - JOUR. T1 - Effects of duration of type 2 diabetes mellitus on insulin secretion. AU - Zangeneh, Farhad. AU - Arora, Puneet S.. AU - Dyck, Peter J.. AU - Bekris, Lynn. AU - Lernmark, Ake. AU - Achenbach, Sara J.. AU - Oberg, Ann L.. AU - Rizza, Robert A.. PY - 2006. Y1 - 2006. N2 - Objective: To gain insight into the effects of duration of type 2 diabetes on insulin secretion in patients with type 2 diabetes mellitus. Methods: C-peptide concentrations were measured every 2 years before and after intravenous injection of 1 mg of glucagon in 89 patients with type 2 diabetes (51 men and 38 women) as part of the Rochester Diabetic Neuropathy Study in those subjects who participated in follow-up (median, 12 years; range, 6 to 14). Results: Although insulin secretion decreased over time (P,0.001) in the group as a whole, both the pattern and the rate of decline in C-peptide concentration differed considerably among the study subjects. Insulin secretion, whether measured as fasting C-peptide, ...

Different people need different types of insulin, so your treatment needs to be tailored to suit you. Your GP-or an endocrinologist-will prescribe the insulin that best suits your lifestyle and blood glucose level targets and advise you on how to use this insulin properly.. The different types of insulin are grouped together based on how long the insulin works in the body. There are five types of insulin (see table below). Insulin can be given as a basal or bolus dose. Basal insulin is a background insulin (intermediate or long acting). Bolus insulin is an ultra-short or short-acting insulin that is usually given with meals.. You may be prescribed more than one type of insulin depending on the type of diabetes you have and your individual management plan. Your insulin needs can also change over time, so its important to have regular reviews of your diabetes management with your GP or CDE. ...

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 ...

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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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 ...

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 ...

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

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

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 ...