| Popis: |
The critical event in physiologic glucose-stimulated insulin secretion is the rise, often oscillatory, in intracellular Ca2+ concentration. This has been assumed to be derived exclusively from variations in Ca2+ influx through voltage-dependent Ca2+ channels as a consequence of glucose-induced block of ATP-sensitive K+ channels. Agents that liberate inositol 1,4,5-triphosphate (eg, carbachol) are well known to release Ca2+ from intracellular stores in β cells and islets. Recently, however, evidence has accumulated suggesting an important role for intracellular Ca2+ sequestration and release by the endoplasmic reticulum in the glucose signaling cascade. Moreover, the filling state of the intracellular Ca2+ stores appears to regulate a novel plasma membrane current (Ca2+ release-activated nonselective cation current, /CRAN) whose activity may control glucose-activated membrane potential oscillations and, indirectly, Ca2+ influx and insulin secretion. In this review we consider the evidence supporting these new paradigms for the regulation of intracellular Ca2+ signaling in the β cell and discuss data implicating lesions in these pathways in the pathogenesis of diabetes mellitus. |
