Expression levels of enzymes generating NO and CO in islets of murine and human diabetes.

The possible implication of the gasotransmitters NO and CO for the development of diabetes remains unresolved. Our previous investigations in rodents suggested NO being inhibitory, and CO stimulatory, to glucose-stimulated insulin secretion (GSIS). Here we studied the possible role of these gasotransmitters in both murine and human type 2 diabetes (T2D) by mapping the expression pattern of neural nitric oxide synthase (nNOS), inducible NOS (iNOS), constitutive heme oxygenase (HO-2), and inducible HO (HO-1) in isolated pancreatic islets.

Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS)-NO system, a negative modulator of glucose-stimulated insulin release.

GPR40 protein levels are crucial to the regulation of stimulated hormone secretion in pancreatic islets. Lessons from spontaneous obesity-prone and non-obese type 2 diabetes in rats.

The role of islet GPR40 protein in the pathogenesis of diabetes is unclear. We explored the influence of GPR40 protein levels on hormone secretion in islets from two rat models of spontaneous type 2 diabetes displaying either hyperlipidaemia or hyperglycaemia. GPR40 expression was analysed by confocal microscopy, Western blot and qPCR in islets from preobese Zucker (fa/fa) rats, diabetic Goto-Kakizaki (GK) rats, and controls.

Pancreatic β-cell dysfunction, expression of iNOS and the effect of phosphodiesterase inhibitors in human pancreatic islets of type 2 diabetes.

Aims: Induction of inducible nitric oxide synthase (iNOS) in pancreatic islets leads to exaggerated nitric oxide (NO) production associated with dysfunctional β-cells. We examined insulin secretion, iNOS expression and its relationship to the cAMP system in islets from human type 2 diabetes.

Methods: Insulin, glucagon and cAMP were analysed by RIA; iNOS or phosphodiesterase (PDE) expression by quantitative PCR (qPCR), Western blot and confocal microscopy; cell viability by MTS.

Abnormally decreased NO and augmented CO production in islets of the leptin-deficient ob/ob mouse might contribute to explain hyperinsulinemia and islet survival in leptin-resistant type 2 obese diabetes.

The role of the gaseous messengers NO and CO for β-cell function and survival is controversial. We examined this issue in the hyperglycemic-hyperinsulinemic ob/ob mouse, an animal model of type 2 obese diabetes, by studying islets from obese vs lean mice regarding glucose-stimulated insulin release in relation to islet NO and CO production and the influence of modulating peptide hormones. Glucose-stimulated increase in ncNOS-activity in incubated lean islets was converted to a decrease in ob/ob islets associated with markedly increased insulin release.