Endogenously produced reactive oxygen species reportedly stimulate insulin secretion from islet β-cells. However, the molecular machinery that governs the oxidant-induced insulin secretion has yet to be determined. The present study demonstrates, using rat islet β-cell-derived RINm5F cells, the involvement of the transient receptor potential (TRP) cation channels in the insulin secretion induce...

In type 2 diabetes mellitus, insulin resistance and an inadequate pancreatic beta-cell response to the demands of insulin resistance lead to impaired insulin secretion and hyperglycemia. Pancreatic duodenal homeodomain-1 (PDX-1), a transcription factor required for normal pancreatic development, also plays a key role in normal insulin secretion by islets. To investigate the role of PDX-1 in isl...

Objective(s): Ghrelin is a peptide hormone that has been shown to have numerous central and peripheral effects. The central effects including GH secretion, food intake, and energy homeostasis are partly mediated by Kiss1- KissR signaling pathway. Ghrelin and its receptor are also expressed in the pancreatic islets. Ghrelin is one of the key metabolic factors controlling insulin secretion from t...

BACKGROUND A current limitation of islet transplantation is reduced long-term graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could improve existing islet function, prevent further loss of islet mass and possibly even stimulate islet regeneration. METHODS This prospective study evaluated the safety, efficacy, and...

The secretion of insulin from pancreatic islet β-cells is critical for glucose homeostasis. Disrupted insulin secretion underlies almost all forms of diabetes, including the most common form, type 2 diabetes (T2D). The control of insulin secretion is complex and affected by circulating nutrients, neuronal inputs, and local signaling. In the current study, we examined the contribution of glycine...

BACKGROUND Our previous studies have shown that signal transducer and activator of transcription 3 (STAT3) signaling is important for the development of pancreatic microvasculature via its regulation of vascular endothelial growth factor-A (VEGF-A). Pancreas-specific STAT3-KO mice exhibit glucose intolerance and impaired insulin secretion in vivo, along with microvascular alterations in the pan...

Glucagon-like peptide 1 (GLP-1) is a hormone that has received significant attention as a therapy for diabetes because of its ability to stimulate insulin biosynthesis and release and to promote growth and survival of insulin-producing beta cells. While GLP-1 is produced from the proglucagon precursor by means of prohormone convertase (PC) 1/3 activity in enteroendocrine L cells, the same precu...

Ghrelin is produced by stomach oxyntic cells and thought to be involved in the regulation of body weight and food intake. We demonstrate here that the peptide inhibits insulin secretion from overnight-incubated mouse islets in the presence of 8.3, 11.1, and 22.2 mmol/liter glucose. Ghrelin was most efficient at 1 nmol/liter and its effect disappeared by raising the dose more than 25 nmol/liter....

We examined the relation between nutrient-stimulated insulin secretion and the islet lysosome acid glucan-1,4-alpha-glucosidase system in rats undergoing total parenteral nutrition (TPN). During TPN treatment, serum glucose was normal, but free fatty acids, triglycerides, and cholesterol were elevated. Islets from TPN-infused rats showed increased basal insulin release, a normal insulin respons...

Insulin-secreting pancreatic islet beta-cells possess anion-permeable Cl- channels (I(Cl,islet)) that are swelling-activated, but the role of these channels in the cells is unclear. The Cl- channel blockers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and niflumic acid were evaluated for their ability to inhibit I(Cl,islet) in clonal beta-cells (HIT cells). Both drugs blocked the cha...