Regulation of Ca2+ homeostasis by islet endoplasmic reticulum and its role in insulin secretion.
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.
Wolf
B A
BA
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Colca
J R
JR
Turk
J
J
Florholmen
J
J
McDaniel
M L
ML
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007425:Intracellular Membranes / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D009994:Osmolar Concentration
D005958:Glucosephosphates; D007328:Insulin; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D002118:Calcium