Suppressed insulin signaling and increased apoptosis in Cd38-null islets

Academic Article

Abstract

  • CD38 is a multifunctional enzyme capable of generating metabolites that release Ca from intracellular stores, including nicotinic acid adenine dinucleotide phosphate (NAADP). A number of studies have led to the controversial proposal that CD38 mediates an alternate pathway for glucose-stimulated insulin release and contributes to the pathogenesis of diabetes. It has recently been shown that NAADP mediates Ca mobilization by insulin in human pancreatic β-cells. In the present study, we report altered Ca homeostasis and reduced responsiveness to insulin, but not glucose, in Cd38 β-cells. In keeping with the antiapoptotic role of insulin signaling, Cd38 islets were significantly more susceptible to apoptosis compared with islets isolated from littermate controls. This finding correlated with disrupted islet architecture and reduced β-cell mass in Cd38 mice, both in the context of a normal lab diet and a high-fat diet. Nevertheless, we did not find robust differences in glucose homeostasis in vivo or glucose signaling in vitro in Cd38 mice on the C57BL/6 genetic background, in contrast to previous studies by others of Cd38 knockout mice on the ICR background. Thus, our results suggest that CD38 plays a role in novel antiapoptotic signaling pathways but does not directly control glucose signaling in pancreatic β-cells. © 2006 by the American Diabetes Association. 2+ 2+ 2+ -/- -/- -/- -/-
  • Published In

  • Diabetes  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 7085778
  • Author List

  • Johnson JD; Ford EL; Bernal-Mizrachi E; Kusser KL; Luciani DS; Han Z; Tran H; Randall TD; Lund FE; Polonsky KS
  • Start Page

  • 2737
  • End Page

  • 2746
  • Volume

  • 55
  • Issue

  • 10