Glucose stimulation of insulin secretion in pancreatic β cells involves cell depolarization and subsequent opening of voltage-dependent Ca2+ channels to elicit insulin granule exocytosis. This pathway alone does not account for the entire magnitude of the secretory response in β cells. In this issue, Ferdaoussi, Dai, and colleagues reveal that insulin secretion is amplified by cytosolic isocitrate dehydrogenase–dependent transfer of reducing equivalents, which generates NADPH and reduced glutathione, which in turn activates sentrin/SUMO-specific protease-1 (SENP1). β Cell–specific deletion of
Alan D. Attie
Triggering and amplification of glucose-stimulated insulin secretion.