Insulin release transduction mechanism through acid glucan 1,4-alpha-glucosidase activation is Ca2+ regulated.
An important signal involved in glucose-stimulated insulin secretion is transduced through the action of a lysosomal acid, glucan 1,4-alpha-glucosidase. We investigated the Ca2+ dependency of this enzyme activity in relation to insulin release. In isolated islets, increased levels of extracellular Ca2+ induced a large increase in acid glucan 1,4-alpha-glucosidase activity accompanied by a similar increase in insulin release at both substimulatory and stimulatory concentrations of glucose. At low glucose the Ca2+ "inflow" blocker nifedipine unexpectedly stimulated enzyme activity without affecting insulin release. However, nifedipine suppressed 45Ca2+ outflow from perifused islets at low glucose and at Ca2+ deficiency when intracellular Ca2+ was mobilized by carbachol. This nifedipine-induced retention of Ca2+ was reflected in increased acid glucan 1,4-alpha-glucosidase activity. Adding different physiological Ca2+ concentrations or nifedipine to islet homogenates did not increase enzyme activity. Neither selective glucan 1,4-alpha-glucosidase inhibition nor the ensuing suppression of glucose-induced insulin release was overcome by a maximal Ca2+ concentration. Hence, Ca(2+)-induced changes in acid glucan 1,4-alpha-glucosidase activity were intimately coupled to similar changes in Ca(2+)-glucose-induced insulin release. Ca2+ did not affect the enzyme itself but presumably activated either glucan 1,4-alpha-glucosidase-containing organelles or closely interconnected messengers.
Salehi
A
A
Department of Pharmacology, University of Lund, Sweden.
Mosén
H
H
Lundquist
I
I
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D005087:Glucan 1,4-alpha-Glucosidase / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D015398:Signal Transduction
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007328:Insulin; D018721:Muscarinic Agonists; D002217:Carbachol; D005087:Glucan 1,4-alpha-Glucosidase; D009543:Nifedipine; D002118:Calcium