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. 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 ...
Rodent studies have demonstrated that insulin action in the CNS can reduce HGP (5,6). Previous human studies that deployed INI at a dose that increases CSF insulin concentration (12) reported changes in peripheral glucose concentration and insulin sensitivity, suggesting CNS insulin may regulate peripheral glucose metabolism (11,14,15). In these studies, however, there was a transient increase in venous insulin concentration after INI administration. The current study is the first human study to definitively demonstrate that INI (40 IU) suppresses EGP compared with INP. Importantly, the experimental design of our study ensured that venous insulin concentrations were similar between treatments.. A 40-IU dose of INI previously caused a rapid increase in CSF insulin concentration (12) without increasing serum insulin. In this study, under conditions of an arterial pancreatic clamp (during which endogenous insulin secretion cannot be modulated), 40 IU of INI (insulin lispro; Eli Lilly Canada) also ...
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 ...
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
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
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 ...
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 ...
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+ ...
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. ...
A role for glucocorticoids (GCs) in the regulation of carbohydrate metabolism and the development of diabetes was first described over 70 years ago. Whilst there is little doubt that systemic GC excess leads to insulin resistance the tissue specific mechanisms underpinning their effect on insulin sensitivity remain to be understood. We have defined tissue specific effects of GCs on insulin sensitivity and lipid metabolism in vitro and in vivo. In skeletal myotubes GCs, in the absence of insulin, decreased glucose uptake and de novo lipogenesis and increased β-oxidation. GC treatment caused insulin resistance, demonstrated by inhibition of insulin signalling and impaired glucose uptake. In human adipocytes, the direct effects of GCs were similar to those in myotubes, with decreased basal glucose uptake and de novo lipogenesis. However, GCs enhanced insulin signalling, insulin-stimulated glucose uptake and de novo lipogenesis. This represents the first description of GC induced insulin ...
Type II diabetic subjects are both insulin-deficient and insulin-resistant. Recent studies suggest that the insulin resistance is due to a combined receptor and postreceptor defect with the postreceptor defect being the predominant lesion. In the present study, we examined the effects of exogenous insulin therapy upon these defects in insulin action in six untreated type II diabetic subjects. Glycemic control and adipocyte insulin binding were measured and in vivo insulin dose-response curves for overall glucose disposal and suppression of hepatic glucose output were constructed before treatment. Following these initial studies, the diabetic subjects were treated with twice-daily injections of regular and NPH purified pork insulin for 14 days and the pretreatment studies repeated. Glycemic control was significantly improved by this treatment regimen. The mean fasting serum glucose level (±SE) fell from 287 ± 20 to 125 ± 13 mg/dl, the mean glycosylated hemoglobin level (± SE) decreased from ...
Mark A. Fishel, M.D., from the University of Washington, Seattle, and colleagues, raised blood insulin levels (while maintaining normal blood sugar levels) in 16 healthy older adults ranging in age from 55 to 81 years, and then measured the changes in levels of inflammatory markers, modulators, and beta-amyloid (a protein associated with AD) in plasma and cerebrospinal fluid.. "Moderate peripheral hyperinsulinemia (increased levels of insulin) provoked striking increases in CNS (central nervous system) inflammatory markers," the authors report. "Our findings suggest that insulin-resistant conditions such as diabetes mellitus and hypertension may increase the risk for AD, in part through insulin-induced inflammation.". "Although this model has obvious relevance for diabetes mellitus, hyperinsulinemia and insulin resistance are widespread conditions that affect many nondiabetic adults with obesity, impaired glucose tolerance, cardiovascular disease, and hypertension. Our results provide a ...
TY - JOUR. T1 - Insulin sensitivity and regional fat gain in response to overfeeding. AU - Votruba, Susanne B.. AU - Jensen, Michael D.. PY - 2011/2. Y1 - 2011/2. N2 - Although insulin resistance and type 2 diabetes (T2DM) are associated with upper body fat distribution, it is unknown whether insulin resistance predisposes to upper body fat gain or whether upper body fat gain causes insulin resistance. Our objective was to determine whether insulin sensitivity predicts abdominal (subcutaneous and/or visceral) fat gain in normal weight adults. Twenty-eight (15 men) lean (BMI = 22.1 2.5kg/m2), healthy adults underwent ∼8 weeks of overfeeding to gain ∼4kg fat. Body composition was assessed before and after overfeeding, using dual-energy X-ray absorptiometry (DXA) and abdominal computed tomography to measure total and regional (visceral, abdominal, and lower body subcutaneous) fat gain. We assessed insulin sensitivity with an intravenous glucose tolerance test (IVGTT) and the 24-h insulin area ...
A flexible insulin regimen is one that lets you adjust the timing and amount of insulin to meet your needs. With a conventional regimen, you take insulin at set times and have to follow a strict schedule. A flexible regimen allows for changes in your schedule and lets you adjust your insulin as needed. For example, you might increase the dose of insulin if you eat a meal with a lot of carbohydrates. Or you might lower your insulin dose if you are going to exercise. A flexible regimen also may help you keep tighter control over your blood sugar level.. A flexible insulin regimen has benefits, but it means you will have to make some extra effort. You must check your blood sugar level regularly and keep track of what you eat. This means counting the carbohydrates you eat. Your nurse, doctor or dietician can teach you how to count carbohydrates. You must also learn how your body reacts to insulin and how to adjust your dose. Too much insulin can give you hypoglycemia (blood sugar level is too low). ...
AIMS/HYPOTHESIS: The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels.. MATERIALS AND METHODS: Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured.. RESULTS: Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic ...
Preterm infants are more likely to have elevated insulin levels at birth and in early childhood compared to full-term infants, find researchers.
The invention relates to a formulation comprising a polypeptide selected from at least one of insulin, an insulin metabolite, an insulin analog, and an insulin derivative; at least one surfactant; optionally at least one preservative; and optionally at least one of an isotonicizing agent, a buffer or an excipient, wherein the formulation is free from or low in zinc. The invention also relates to the production of such insulin preparations and their use as pharmaceutical formulations.
The Minimed 512 and the Deltec Cozmo both calculate "insulin on board" when , , suggesting adjustments, so as not to stack insulin. The Minimed uses a scale , , that approximates insulin activity based on manufacturer data (90% of the , , insulin activity left after one hour, 65% left after two hours, 43% after , , three hours, and 24% of the activity working between hours four and eight), , , whereas the Cozmo uses a straight line from zero hours to the number of hours , , the user specifies (if the user specifies four hours, then 75% after one , hour, , , 50% after two hours, 25% after three hours, and 0% after four hours). , , , , At first glance it seems that the Minimed method is superior, since it , , approximates actual insulin activity, rather than a straight line. But is it , , really? When calculating "insulin on board" does one really want to estimate , , insulin _activity_ or insulin that is _unabsorbed_ (or ar they the same , , thing)? That is, even if the insulin activity doesnt ...
The mechanism(s) linking physical inactivity, obesity, and type-II diabetes are unclear. I hypothesized low intrinsic aerobic capacity is associated with reduced systemic insulin sensitivity via skeletal muscle insulin signaling. After 34 generations of selective breeding, high aerobic capacity (HCR) rats exhibited an 8-fold increase in running distance vs low aerobic capacity (LCR) rats (n=14 per group). LCR rats had higher rates of weight gain vs HCR (p|0.05) though food consumption was constant (p=0.86) over a 12-week study. Rats were divided into 4 groups: 1) LCR-Sham Surgery, 2) LCR-Catheterization, 3) HCR-Sham Surgery or 4) HCR-Catheterization (n=7 per group). Euglycemic-hyperinsulinemic clamps on catheterized rats tested insulin sensitivity while sham LCR and HCR were used for basal tissue analysis. Plasma insulin levels did not differ during the clamps, but LCR required lower glucose infusion rates than HCR (p|0.05). Upon insulin stimulation, both absolute and normalized phospho-Akt(Ser473) of
TY - JOUR. T1 - Autocrine insulin increases plasma membrane KATP channel via PI3K-VAMP2 pathway in MIN6 cells. AU - Xu, Shanhua. AU - Kim, Ji Hee. AU - Hwang, Kyu Hee. AU - Das, Ranjan. AU - Quan, Xianglan. AU - Nguyen, Tuyet Thi. AU - Kim, Soo Jin. AU - Cha, Seung Kuy. AU - Park, Kyu Sang. PY - 2015/12/25. Y1 - 2015/12/25. N2 - Regulation of ATP-sensitive inwardly rectifying potassium (KATP) channel plays a critical role in metabolism-secretion coupling of pancreatic β-cells. Released insulin from β-cells inhibits insulin and glucagon secretion with autocrine and paracrine modes. However, molecular mechanism by which insulin inhibits hormone secretion remains elusive. Here, we investigated the effect of autocrine insulin on surface abundance of KATP channel in mouse clonal β-cell line, MIN6. High glucose increased plasmalemmal sulfonylurea receptor 1 (SUR1), a component of KATP channel as well as exogenous insulin treatment. SUR1 trafficking by high glucose or insulin was blocked by ...
Type 2 diabetes mellitus is a complex metabolic disorder characterized by abnormal insulin secretion and glucose homeostasis, resulting from impaired pancreatic beta-cell function and insulin resistance in target tissues. The worldwide prevalence of type 2 diabetes mellitus is reaching epidemic proportions, and the total number of cases is expected to reach 221 million by 2010. The high incidence of the disease and its associated complications places a significant burden on healthcare systems.. The primary risk factor for the development of type 2 diabetes mellitus is obesity and its associated insulin resistance. Insulin resistance is characterized by an impaired response to the physiologic effects of insulin and leads to decreased cellular glucose uptake, increased hepatic gluconeogenesis, and a compensatory increase in insulin secretion that contributes to beta-cell exhaustion. Therefore in the insulin-resistant state, blood glucose and insulin levels are increased. The relationship between ...
Glucose Glucose concentration was determined by a hexokinase method. It is an endpoint enzymatic method with a sample blank correction. Insulin Insulin is the primary hormone responsible for controlling glucose metabolism, and its secretion is determined by plasma glucose concentration. The insulin molecule is synthesized in the pancreas as pro-insulin and is later cleaved to form C-peptide and insulin. The principal function of insulin is to control the uptake and utilization of glucose in the peripheral tissues. Insulin concentrations are severely reduced in insulin-dependent diabetes mellitus (IDDM) and some other conditions, while insulin concentrations are raised in non-insulin-dependent diabetes mellitus (NIDDM), obesity, and some endocrine disorders. The Merocodia Insulin ELISA is a two-site enzyme immunoassay utilizing the direct sandwich technique with two monoclonal antibodies directed against separate antigenic determinants of the insulin molecule. Specimen, control, or standard is ...
Diabetes mellitus (sugar diabetes) is a condition in which the body does not make enough insulin to meet its needs or does not properly use the insulin it makes. Without insulin, glucose cannot get into the bodys cells. Without glucose, the cells will not work properly.. To work properly, the amount of insulin you use must be balanced against the amount and type of food you eat and the amount of exercise you do. If you change your diet, your exercise, or both without changing your insulin dose, your blood glucose level can drop too low or rise too high. A prescription is not necessary to purchase most insulin. However, your doctor must first determine your insulin needs and provide you with special instructions for control of your diabetes. Insulin can be obtained from beef or pork pancreas glands. Another type of insulin that you may use is called human insulin. It is just like the insulin made by humans but it is made by methods called semi-synthetic or recombinant DNA. All types of insulin ...
Background: Circulating insulin levels have been positively associated with risk of colorectal cancer; however, it remains unclear whether a diet inducing an elevated insulin response influences colorectal cancer risk. On the basis of a novel insulin index for individual foods, we estimated insulin demand for overall diets and assessed its association with colorectal cancer in the Nurses Health Study and Health Professionals Follow-up Study.. Methods: We followed 86,740 women and 46,146 men who were free of cancer and diabetes at baseline and identified a total of 2,481 colorectal cancer cases during up to 26 years of follow-up. Dietary insulin load was calculated as a function of food insulin index and the energy content of individual foods was reported on food frequency questionnaires. Average dietary insulin index was calculated by dividing the dietary insulin load by the total energy intake.. Results: Dietary insulin load and dietary insulin index were not associated with risk of colorectal ...
There seems to be a lot of misinformation on the internet and through word of mouth regarding cancer and how sugar and insulin interact with tumors. Ive even heard bad information passed from health care providers on to cancer patients. When it comes to sugar, insulin and cancer you have to know the facts!. Insulin Basics. Insulin is a protein hormone produced in your body. After eating any kind of carbohydrate (found in desserts, sweetened drinks, fruits, milk, grains and starchy vegetables), the pancreas produces insulin to move glucose (blood sugar) from the blood into cells all over the body. Glucose is what gives our cells energy to work; they cannot function without it.. If the cells do not respond to insulin, then the pancreas compensates by making even more insulin in order to force the cells to respond. As time goes on, it can take more and more insulin for the cells to take in glucose. In many undiagnosed pre-diabetes cases, blood sugars can measure normal but insulin levels are ...
TY - JOUR. T1 - Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics). AU - Kang, Taewook. AU - Jensen, Pia. AU - Huang, Honggang. AU - Christensen, Gitte Lund. AU - Billestrup, Nils. AU - Larsen, Martin Røssel. PY - 2018. Y1 - 2018. N2 - Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. However, the molecular mechanisms underlying the insulin secretion are unclear. Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for ...
In our study, chronic HF feeding was used to induce obesity in male C57BL/6 mice, which were then subjected to 3 weeks of switching to NC or 40 % CR to induce weight loss. Our findings demonstrated that moderate (40 %) CR to achieve normal weight could reverse β-cell dysfunction and insulin resistance, and restore glucose tolerance in DIO mice. The activation of β-cell autophagy might participate in this process.. After 12 weeks of HF feeding, HF AL mice became remarkably obese, and showed glucose intolerance and insulin resistance, accompanying by hypertrophic islets and increased β-cell area. Moreover, their early-phase insulin secretion tended to decrease and second-phase insulin secretion elevated significantly in vivo. This phenomenon is also commonly observed in patients with IGT (impaired glucose tolerance) or early-stage T2DM. Ex vivo isolated islets had increased insulin content and defective insulin secretion that manifested as enhanced basal insulin secretion and reduced high ...
Background. The two main types of diabetes are type 1 (formerly called insulin-dependent diabetes) and type 2 (formerly called non-insulin-dependent diabetes). In type 1, insulin is always required because the insulin-producing islet cells in the pancreas have been destroyed. In type 2, the pancreas can still produce insulin, and treatment is initially with diet and exercise, but the disease often progresses, with deteriorating control and rising blood glucose levels, and a need next for oral hypoglycaemic agents (OHAs), and later for insulin in about 30%. The aim of insulin therapy is to reduce blood glucose to normal levels, without going too low and causing hypoglycaemia.. Insulin currently has to be given by injection. There are various types according to duration of action - short, intermediate and long. Short- and long-acting insulin both come in two forms: traditional and the newer analogues. The traditional form of short-acting insulin is known as soluble. It is given by injection using ...
Other factors can contribute in any individual (e.g., glucocorticoid-induced insulin resistance) that may require specific additional treatment.. Current Treatment Strategies. Given the previous knowledge of factors affecting insulin secretion and insulin resistance, therapy should be aimed at. 1. Reducing factors known to cause insulin resistance - obesity, physical inactivity, concurrent illnesses, drug therapies. 2. Addressing factors that promote insulin secretion - decrease amyloid deposition by providing insulin, decrease hyperglycaemia and hypertriglyceridaemia through the use of potent hypoglycaemic agents (e.g., insulin), provide an appropriate diet. In the newly diagnosed but healthy diabetic cat, treatment usually surrounds insulin administration and dietary control. However, the intensity of the monitoring strategy has implications for frequency of dosing changes and outcome.. Insulin Preparations. A wide variety of insulin preparations are available for maintenance therapy and ...