View clinical trials related to Insulin Secretion.
Filter by:This trial investigates the effect of BurstDR and tonic spinal cord stimulation (SCS) on glucose metabolism and heart rate variability in patients with neuropathic pain.
Oral supplementation with highly bioavailable forms of iron, such as ferrous sulphate, is the treatment of choice for iron-deficiency anemia. Iron from ferrous sulphate is efficiently absorbed in the duodenum, resulting in a rapid increase in transferrin saturation and appearance of "free iron" or non-transferrin bound iron (NTBI) in blood. NTBI is highly reactive and can catalyze the generation of reactive oxygen species and cause oxidative tissue damage. Human pancreatic beta cells are known to express ZIP14, a transporter that has been implicated in uptake of NTBI from blood. In vitro and animal studies have shown that iron loading in beta cells can result in impaired insulin secretion. However, there are no human studies that have looked at the acute effects of oral iron intake on insulin secretion. In this study, we plan to look at the effect of a single oral dose of ferrous sulphate on insulin secretion kinetics in healthy individuals. A single arm before-and-after (pre-post) study design will be used. Consenting individuals who meet the participation criteria will undergo a 75g oral glucose tolerance test (OGTT) to document baseline insulin secretion kinetics. One week later, OGTT will be repeated after administering a single dose of ferrous sulphate (120 mg of elemental iron) 2 hours prior to the test. Iron-induced change in insulin secretion kinetics will be documented. In addition, we will determine changes in glucose tolerance, insulin resistance and insulin clearance rates.
Type 2 diabetes (T2D) mellitus is a challenge for health care systems as the numbers increases constantly. In 2014, 422 million people had been living with diabetes worldwide. The absolute numbers of people with prediabetes have also grown substantially over 25 years worldwide. In Germany, about 10% of the population has T2D and another 21 % of the population has prediabetes.Overall, 16% of all deaths in Germany are attributable to type 2 diabetes. Macro- and microvascular complications of diabetes imply a significant threat for the patients and are already present in the prediabetic state. Short term and long term complications, the burden of treatment, and reduced quality of life are major burdens of the disease. Accumulating data indicate that currently recommended therapeutic diet regimens in patients with obesity and diabetes are not sustainable on the long term. Novel concepts are therefore urgently needed. T2D occurs when insulin secretion from pancreatic beta-cells cannot sufficiently be increased to compensate for insulin resistance. Causes of beta-cell dysfunction are heterogeneous. In addition, the most important determinants of diabetes remission are the extend of weight loss and restoration of beta-cell function. In the course of diabetes progression, the inability to recover insulin secretion might identify the state of no return to normal glucose tolerance. It is therefore crucial to improve insulin secretion in treatment and prevention of diabetes. Up to now lifestyle intervention trials in prediabetes or pharmacological intervention trials in diabetes did not show improvement of insulin secretion after intervention. However, one recent small human trial shows that intermittent fasting (early time restricted fasting) is able to improve insulin secretion.Currently, there are no trials that examine the effect of intermittent fasting in individuals with a broad range of impaired glucose metabolism (from prediabetes to diabetes). Recently novel subtypes of diabetes and prediabetes with high risk for the early manifestation of diabetes complications have been identified. Currently, prevention strategies for this high risk individuals have not been examined yet. We will study for the first time the effectiveness of 4 weeks intermittent fasting on changes in insulin secretion capacity in subphenotypes of diabetes and in prediabetes.
Glucagon is a 30 amino acid peptide hormone that is produced exclusively in alpha-cells of the pancreatic islets. Glucagon binds to a G-protein coupled receptor and activates intracellular signaling by increasing the synthesis of cyclic AMP by adenylate cyclase. The glucagon receptor is most prominently expressed by hepatocytes and the cardinal action of glucagon is to stimulate hepatic glucose output by increasing glycogenolysis and gluconeogenesis. A deep body of literature supports physiologic actions of glucagon to maintain fasting blood glucose and counter-regulate hypoglycemia, and the current view of glucose metabolism is that insulin and glucagon have opposing and mutually balancing effects on glycemia. However, it has long been appreciated that glucagon actually stimulates insulin secretion and islet β-cells express the glucagon receptor and respond to its activation by increasing cAMP. The most potent stimulus for glucagon release is hypoglycemia and both low glucose per sé, as well as sympathetic nervous system activity are potent activators of the alpha-cell. However, glucagon is also stimulated by elevations of circulating amino acids, including after protein containing meals; this setting is one in which the release of glucagon during a period of elevated glycemia could contribute to postprandial insulin secretion. In fact, we have demonstrated that normal mice injected with glucagon while fasting (BG 75 mg/dl) have a prompt rise in blood glucose, whereas mice given glucagon while feeding (BG 150 mg/dl) increase insulin output 3 fold and have a decrease in glycemia. Moreover, in studies with isolated mouse and human islets we have demonstrated that glucagon stimulates insulin release by activating both the glucagon and GLP-1 receptors. This counter-intuitive observation has been reported by several other groups as well as ours. In the studies proposed herein we wish to extend our novel observations to humans. The possibility that glucagon acts in the fed state to promote insulin secretion and glucose disposal would change current views of physiology in both healthy and diabetic persons. Moreover, since one of the more promising area of drug development is the creation of peptides that activate multiple receptors (GLP-1 + glucagon, GLP-1 + GIP + glucagon) the results of our studies have potential implications for therapeutics as well.
Dyslipidemia is characterized by low levels of HDLs, hypertriglyceridemia as well as an increases proportion of small dense LDLs. Changes in lipoprotein particles and its concentrations, especially increased levels of pro-atherogenic LDL particles play an important role in the development of cardiovascular diseases. It is well established that statin/PCSK9-inhibitor treatment is very effective in lowering LDL cholesterol levels and therefore in preventing cardiovascular events. Besides the beneficial effects on cardiovascular system, these therapies are unfortunately linked to increased risk for type 2 diabetes. However underlying mechanisms for the association between LDL cholesterol levels and the risk for type 2 diabetes remains largely unknown.Type 2 diabetes is especially characterized by insulin resistance and impaired insulin secretion from pancreatic beta-cells. Insulin resistance alone is insufficient to cause type 2 diabetes, as long as the ß-cell is able to compensate for the increased demand for insulin. Once this compensatory mechanism reaches its physiological limits, individuals progress to type 2 diabetes. Accordingly we aimed to investigate the associations between LDL cholesterol concentrations and the key issue in the pathogenesis of type 2 diabetes, insulin secretion before and after lowering cholesterol concentration by treatment with Evolocumab for 12 weeks in patients with medical indication for a treatment with a PCSK9-inhibitor. Therefore, patients will either undergo a hyperglycemic clamp or a oral glucose tolerance test in randomized manner.
Insulin resistance is a central pathophysiological component of type 2 diabetes and is associated with a high risk of cardiovascular disease. The tissue in which it manifests are mainly muscle, liver, and adipose tissue. Since the transport of glucose to the brain is independent of insulin, this organ has traditionally not been studied in this regard. In animal experiments, however, knockout of the insulin receptor in the brain leads to obesity and peripheral insulin resistance. This finding of insulin action in the brain could also be confirmed in human studies. The investigators intend to investigate whether central nervous insulin action affects insulin secretion in humans. For this purpose, nasal insulin and placebo are administered 15 minutes before a hyperglycemic hyperinsulinemic clamps, which stimulate insulin secretion. Insulin sensitivity of the brain is measured by a an established protocol with functional magnetic resonance imaging before and after nasal insulin administration.
AIM2: The purpose of Aim-2 of this study is to determine the role of basal GLP-1 action on the beta-cell response to insulin resistance. Healthy subjects will have fasting GLP-1 action determined with GLP-1r blockade before and after induction of experimental insulin resistance. The investigators hypothesize that fasting GLP-1 action will increase to compensate for experimental insulin resistance. AIM3: The purpose of Aim-3 of this study is to determine the role of basal GLP-1 action on fasting glucose regulation in lean, obese, pre-diabetic and type 2 diabetic (T2DM) subjects. A cross sectional study of age-matched subjects across the spectrum of glucose tolerance will be used to test the hypothesis that fasting GLP-1 action increases as beta-cell function declines.
Our studies are aimed at examining effects of intrauterine exposure to GDM on metabolic risks in Hispanic children. Our primary hypothesis predicts that intrauterine exposure to GDM will be associated with one or more of three critical factors involved in the development of diabetes: 1) increased adiposity, 2) insulin resistance, and 3) decreased beta cell function in Hispanic children when compared to non-exposed children matched for ethnicity, age, gender, and Tanner stage. In a subset of this cohort, we will also examine the effects of intrauterine exposure to gestational diabetes on the brain pathways that regulate appetite and body weight in children ages 6 to 15 years old.
This project is designed to advance understanding of the incretin effect in health and disease. This system of gut-islet linkage is essential for normal glucose tolerance, impaired in T2DM, and amenable to therapeutic intervention. However, there are important gaps in understanding incretin function that limit application of this system; this project will address several of these. A secondary, but critical aspect of this research is focus on inter-individual variation in the physiology of the incretin system. This is a novel direction for research in this field and is critical to advancing the concept of individualized medical care in diabetes by establishing whether there is a physiologic basis for predicting the existence of responders and non-responders to incretin therapies. Currently, we have described only Aim 1 from this grant in this protocol registration. While Aim 2 and 3 are described in the grant, Aim 1 will be conducted first and the results from this Aim and / or the publication of other results in the field may affect the approach to Aims 2 and 3.
1. The purpose of this study is to determine whether Sitagliptin therapy suppress glucagon release and improve glucose control in Chinese type 2 diabetic. 2. There are different effects of Sitagliptin therapy on blood glucose regulation, pancreatic alpha & beta cell function are different in lean (BMI<25) and overweight (BMI>25) Chinese type 2 diabetics. 3. The purpose of this study is to determine whether glucagon release may contribute over 30% to the hyperglycemia in Chinese type 2 diabetics.