Nuclear Factor-κB Activity in β-Cells Is Required for Glucose-Stimulated Insulin Secretion

Abstract

Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells depends on coordinated glucose uptake, oxidative metabolism, and Ca²⁺-triggered insulin exocytosis. Impaired GSIS is a hallmark of type 2 diabetes. However, at present we know very little about the molecular mechanisms that induce and maintain the expression of genes required for GSIS in β-cells. The transcription factor nuclear factor-κB (NF-κB) is activated by an increase in intracellular Ca²⁺ in β-cells. Here, we show that attenuation of NF-κB activation in β-cells generates mice with impaired GSIS, and that the β-cells show perturbed expression of genes required for glucose uptake, oxidative metabolism, and insulin exocytosis. Thus, NF-κB appears to be part of a positive regulatory circuit that maintains GSIS in pancreatic β-cells.