AJP - Endocrinology and Metabolism, Vol 254, Issue 2 E121-E136, Copyright © 1988 by American Physiological Society

ARTICLES

Regulation of Ca2+ homeostasis by islet endoplasmic reticulum and its role in insulin secretion

B. A. Wolf, J. R. Colca, J. Turk, J. Florholmen and M. L. McDaniel
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.

Changes in intracellular Ca2+ concentrations have a major role in the regulation of insulin secretion by islet beta-cells. It has recently become apparent that the endoplasmic reticulum plays a prominent role in the regulation of intracellular Ca2+ concentrations under basal conditions and during insulin secretion. This review describes biochemical properties of the endoplasmic reticulum that contribute to intracellular Ca2+ homeostasis including 1) an ATP-dependent Ca2+ uptake pump associated with a Ca2+-ATPase located in the endoplasmic reticulum; 2) Ca2+ release from the endoplasmic reticulum induced by the second messengers inositol trisphosphate and arachidonic acid as well as the guanine nucleotide GTP; and 3) a Ca2+ sequestration mechanism localized to the endoplasmic reticulum that is regulated by glucose 6-phosphate and glucose-6-phosphatase. The hypothesis is developed that these biochemical mechanisms participate in the regulation of intracellular Ca2+ concentrations and represent central intracellular events involved in the first phase of glucose-induced insulin secretion.

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