Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", ...

Abstract Reactive oxygen species and oxidative stress impair β-cell function and reduce insulin secretion. It has been shown that progesterone and cilostazol possess antioxidant properties. The present study was aimed to investigate in vitro pretreatment effect of progesterone and cilostazol on insulin secretion as well as their protective effects against hydrogen peroxide-induced oxidative str...

OBJECTIVE Fructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme that is upregulated in islets or pancreatic beta-cell lines exposed to high fat. However, whether specific beta-cell upregulation of FBPase can impair insulin secretory function is not known. The objective of this study therefore is to determine whether a specific increase in islet beta-cell FBPase can result in reduced gl...

Nitric oxide (NO) produced by islet constitutive NO synthase (cNOS) is a putative modulator of islet hormone secretion. We show here for the first time that the release of insulin induced byl-arginine orl-homoarginine is inhibited and that of glucagon stimulated in parallel with the rate of islet NO production. It was found thatl-homoarginine was ≈25-30% less potent thanl-arginine as an insulin...

Soluble epoxide hydrolase (sEH) is an enzyme involved in the metabolism of endogenous inflammatory and antiapoptotic mediators. However, the roles of sEH in diabetes and the pancreas are unknown. Our aims were to determine whether sEH is involved in the regulation of hyperglycemia in diabetic mice and to investigate the reasons for the regulation of insulin secretion by sEH deletion or inhibiti...

Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin s...

Still not clearly defined is the fundamental defect or defects involved in the pathogenesis of type II noninsulin-dependent diabetes mellitus. Abnormalities in both insulin secretion and insulin action have been demonstrated, and there has been considerable debate as to which is the predominant lesion. During the 1970s, with the evolution of the concept of two major types of diabetes—type I and...

We measured in vivo and in vitro nutrient-stimulated insulin secretion in late gestation fetal sheep to determine whether an intrinsic islet defect is responsible for decreased glucose-stimulated insulin secretion (GSIS) in response to chronic hypoglycemia. Control fetuses responded to both leucine and lysine infusions with increased arterial plasma insulin concentrations (average increase: 0.1...

OBJECTIVE Roux-en-Y gastric bypass surgery (GB) is characterized by accentuated but short-lived postprandial elevations of blood glucose and insulin. This profile has been attributed to effects of relative hyperglycemia to directly stimulate β-cells and an augmented incretin effect. An additional glucose-independent stimulation of insulin secretion in GB subjects was hypothesized. METHODS Fif...

An improved method for the isolation of rat pancreatic islets possessing adenylate cyclase responsive to various hormones and agents is described. The key step in this method, which yielded up to 500 islets per pancreas, involved pretreatment of rats with pilocarpine. This allowed depletion of zymogens from the exocrine pancreatic tissue and thus minimized the destruction of islet membranal str...