Calcium and the Control of Insulin Secretion

Oscillatory control of insulin secretion

“…It has been known for more than 40 years that extracellular Ca 2+ is a prerequisite for glucosestimulated insulin secretion (Grodsky and Bennett, 1966;Milner and Hales, 1967) and numerous later studies have emphasized the fundamental role of Ca 2+ in the insulin secretory process (Wollheim and Sharp, 1981;Hellman and Gylfe, 1986b;Ashcroft and Rorsman, 1989). Ca 2+ stimulates insulin secretion by regulating docking and initiating fusion of secretory granules with the plasma membrane, a process mediated by SNARE proteins (Rorsman and Renström, 2003;MacDonald and Rorsman, 2007).…”

Glucose Regulation of Free Ca2+ in the Endoplasmic Reticulum of Mouse Pancreatic Beta Cells

“…2ϩ is a key regulator of many cellular functions including the release of insulin from pancreatic beta cells (1,2). After the introduction of membrane-permeable fluorescent indicators a number of studies have provided important information about cytoplasmic Ca 2ϩ in the beta cell (3).…”

“…Early studies with 45 Ca indicated that glucose, in addition to stimulating the entry of Ca 2ϩ into the beta cells, promotes the sequestration of the ion in an inositol 1,4,5-trisphosphate-(IP 3 ) sensitive pool (18). Because Ca 2ϩ accumulation in the ER is required both for Ca 2ϩ homeostasis of the beta cell (20 -22) and the proinsulin handling (23), it is important to explore whether sequestration of this ion is actively regulated by ATP produced during glucose metabolism (2) or simply reflects the elevation of cytoplasmic Ca 2ϩ (13). Using the furaptra approach we now demonstrate that glucose is an efficient stimulator of Ca 2ϩ uptake in the ER of the pancreatic beta cell both by increasing ATP and cytoplasmic Ca 2ϩ .…”

“…Glucose, the major natural stimulator of insulin release, has profound effects on the beta cell handling of Ca 2ϩ (18,19). Early studies with 45 Ca indicated that glucose, in addition to stimulating the entry of Ca 2ϩ into the beta cells, promotes the sequestration of the ion in an inositol 1,4,5-trisphosphate-(IP 3 ) sensitive pool (18).…”

Signaling Underlying Pulsatile Insulin Secretion

“…The cytoplasmic Ca2+ concentration ([Ca2+],) is probably the most important determinant of insulin secretion [41,831. Measuring [Ca2+], in individual mouse p-cells stimulated with glucose we discovered in 1988, that Ca2+ signalling is oscillatory with a periodicity of 2-6 min ( Fig.…”