title: Islet oxygen consumption and insulin secretion tightly coupled to calcium derived from L-type calcium channels but not from the endoplasmic reticulum.
abstract: The aim of the study was to test whether the source of intracellular calcium (Ca2+) is a determinant of beta cell function. We hypothesized that elevations in cytosolic Ca2+ caused by the release of Ca2+ from the endoplasmic reticulum (ER) have little physiologic impact on oxygen consumption and insulin secretion. Ca2+ release from the ER was induced in isolated rat islets by acetylcholine and response of oxygen consumption rate (OCR), NAD(P)H, cytosolic Ca2+, and insulin secretory rate (ISR) were measured. Glucose increased all four parameters, and thereafter acetylcholine further increased cytosolic Ca2+, OCR, and ISR. To assess the contribution of Ca2+ release from the ER in mediating the effects of acetylcholine, ER Ca2+ stores were first emptied by inhibiting the sarcoendoplasmic reticulum Ca2+-ATPase, which subsequently reduced the effect of acetylcholine on cytosolic Ca2+ but not its effects on OCR or ISR. As predicted, OCR and ISR were acutely sensitive to changes in L-type Ca2+ channel activity; nimodipine completely inhibited glucose-stimulated ISR and suppressed OCR by 36%, despite only inhibiting cytosolic Ca2+ by 46%. Moreover, in the presence of nimodipine and high glucose, acetylcholine still elevated cytosolic Ca2+ levels above those observed in the presence of high glucose alone but did not significantly stimulate ISR. In conclusion, Ca2+ flux through L-type Ca2+ channels was tightly coupled to changes in OCR and ISR. In contrast, the results obtained support the notion that Ca2+ release from the ER has little or no access to the intracellular machinery that regulates OCR and ISR.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Merle
authors.initials: M
authors.lastname: Gilbert
authors.forename: Seung-Ryoung
authors.initials: SR
authors.lastname: Jung
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Reed
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sweet
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D011913:Rats, Inbred BB; D046509:Tissue Culture Techniques
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D018678:Cholinergic Agents; D007328:Insulin; D009553:Nimodipine; D005947:Glucose; D000109:Acetylcholine; D002118:Calcium