GLP-1 (glucagon-like peptide 1) and its mimetic exendin-4 are used against Type 2 diabetes. C-peptide has also proven promising to enhance insulin action. Since insulin secretion in vivo can be rapidly tuned by changes in islet microcirculation, we evaluated the influence of GLP-1, exendin-4 and C-peptide on pancreatic IBF (islet blood flow), and dynamic changes in insulin secretion and glycaem...

y-Aminobutyric acid (GABA), a prominent inhibitory neurotransmitter, is present in high concentrations in p-cells of islets of Langerhans. The GABA shunt enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T), have also been localized in islet p-cells. With the recent demonstration that the 64,000-M, antigen associated with insulin-dependent diabetes mellitus is GAD, there is inc...

The aim of this study was to assess whether cadherin-mediated adhesion of human islet cells was affected by insulin secretagogues and explore the role of cadherins in the secretory activity of β-cells. Experiments were carried out with single islet cells adherent to chimeric proteins made of functional E-, N-, or P-cadherin ectodomains fused to the Fc fragment of immunoglobulin (E-cad/Fc, N-cad...

We examined whether the additional demand for insulin secretion imposed by dietary saturated fatinduced insulin resistance during pregnancy is accommodated at late pregnancy, already characterised by insulin resistance. We also assessed whether effects of dietary saturated fat are influenced by PPARα activation or substitution of 7% of dietary fatty acids (FA) with long-chain ω3 FA, manipulatio...

Many factors influence the outcome of islet transplantation. As islets in the early posttransplant setting are supplied with oxygen by diffusion only and are in a hypoxic state in the portal system, we tested whether small human islets are superior to large islets both in vitro and in vivo. We assessed insulin secretion of large and small islets and quantified cell death during hypoxic conditio...

In insulin-resistant status such as obesity, failure of pancreatic islets to increase insulin secretion leads to diabetes. We sought to screen for the islet genes that facilitate islet adaptation to obesity by comparing gene expression profiles between two strains of obesity-prone inbred mice with different propensities for hyperglycemia. C57BL/6J and AKR/J were fed regular rodent chow or high-...

The abilities of glucose, mannose, and fructose to serve as substrates for glycolysis were compared with the potencies of these hexoses to stimulate hormone secretion. Glucose and mannose induced insulin release at threshold levels of 4 and 10 mM and were effective half-maximally at 8 and 15 mM, respectively. Maximal release with glucose and mannose occurred at 15 and 20 mM, respectively. At th...

Introduction The control of insulin secretion by the islet of Langerhans /?-cell is not fully understood. Nutrients, circulating hormones, neural and autocrine (produced by the /?-cell itself)/paracrine (produced by other islet cell types) mechanisms all apparently have an influence. Inhibitory mechanisms are important to ensure an equal cell response to stimulatory factors and thus protect ind...

Emerging evidence suggests that GTP-binding proteins (G proteins) play important regulatory roles in physiological insulin secretion from the islet beta-cell. Such conclusions were drawn primarily from experimental data derived through the use of specific inhibitors of G protein function. Data from gene depletion experiments appear to further substantiate key roles for these signaling proteins ...

Aims/hypothesisType 2 diabetes (T2D) is characterized by a progressive loss of beta-cell function, and the “disappearance” beta-cells in T2D may also be caused process beta -cell dedifferentiation. Since noradrenergic innervation inhibits insulin secretion density fibers increased type mouse models, we aimed to study relation between islet innervation, dedifferentiation function humans.MethodsU...