title: Nuclear factor-{kappa}B activity in {beta}-cells is required for glucose-stimulated insulin secretion.
abstract: Glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells depends on coordinated glucose uptake, oxidative metabolism, and Ca(2+)-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 beta-cells. The transcription factor nuclear factor-kappaB (NF-kappaB) is activated by an increase in intracellular Ca(2+) in beta-cells. Here, we show that attenuation of NF-kappaB activation in beta-cells generates mice with impaired GSIS, and that the beta-cells show perturbed expression of genes required for glucose uptake, oxidative metabolism, and insulin exocytosis. Thus, NF-kappaB appears to be part of a positive regulatory circuit that maintains GSIS in pancreatic beta-cells.
authors.affiliation: Umeå Center for Molecular Medicine, University of Umeå, S-901 87 Umeå, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Norlin
authors.forename: Ulf
authors.initials: U
authors.lastname: Ahlgren
authors.forename: Helena
authors.initials: H
authors.lastname: Edlund
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D020672:I-kappa B Proteins; D007328:Insulin; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D005947:Glucose