Chronic antidiabetic sulfonylureas in vivo: reversible effects on mouse pancreatic beta-cells.

ABSTRACT:

Background

Pancreatic beta-cell ATP-sensitive potassium (K ATP) channels are critical links between nutrient metabolism and insulin secretion. In humans, reduced or absent beta-cell K ATP channel activity resulting from loss-of-function K ATP mutations induces insulin hypersecretion. Mice with reduced K ATP channel activity also demonstrate hyperinsulinism, but mice with complete loss of K ATP channels (K ATP knockout mice) show an unexpected insulin undersecretory phenotype. Therefore we have proposed an "inverse U" hypothesis to explain the response to enhanced excitability, in which excessive hyperexcitability drives beta-cells to insulin secretory failure without cell death. Many patients with type 2 diabetes treated with antidiabetic sulfonylureas (which inhibit K ATP activity

SUBMITTER: Remedi MS 

PROVIDER: S-EPMC2573909 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature