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Nuclear Factor-B Activity in ß-Cells Is Required for Glucose-Stimulated Insulin Secretion

From the Umeå Center for Molecular Medicine, University of Umeå, Umeå, Sweden

Glucose-stimulated insulin secretion (GSIS) in pancreatic ß-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 ß-cells. The transcription factor nuclear factor-B (NF-B) is activated by an increase in intracellular Ca²⁺ in ß-cells. Here, we show that attenuation of NF-B activation in ß-cells generates mice with impaired GSIS, and that the ß-cells show perturbed expression of genes required for glucose uptake, oxidative metabolism, and insulin exocytosis. Thus, NF-B appears to be part of a positive regulatory circuit that maintains GSIS in pancreatic ß-cells.

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