Increase in cAMP Levels in β-Cell Line Potentiates Insulin Secretion Without Altering Cytosolic Free-Calcium Concentration

Author:

Hill Ronald S1,Oberwetter James M1,Boyd Aubrey E1

Affiliation:

1. Departments of Medicine and Cell Biology, Baylor College of Medicine Houston, Texas

Abstract

With an SV40-transformed hamster β-cell line (HIT cells) as a model system, we tested the hypothesis that a rise in cAMP levels potentiates insulin release by an effect on the cytosolic free-Ca2+ concentration ([Ca2+])i. Intracellular cAMP levels were measured by radioimmunoassay, and ([Ca2+])i was monitored with the fluorescent Ca2+ indicator quin 2. Insulin secretion was followed in static incubations or perifusion of the cells. In perifusion, both high glucose and depolarization of the β-cell with 40 mM K+ trigger a monophasic pattern of insulin release without altering the HIT cell cAMP content. Addition of either the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) or the adenylate cyclase activator forskolin dramatically increased the cellular cAMP content, potentiated the burst phase of insulin release, and coupled the immediate phase of insulin secretion to a sustained secretory response. However, increases in cellular cAMP content were not associated with a change in ([Ca2+])i,. Thus, the potentiation of insulin secretion by a rise in cAMP in the HIT cell is not mediated by a release of stored Ca2+. Either a glucose-generated signal or a rise in ([Ca2+])i triggered by high K+ can synergize with a rise in cAMP to couple the burst or immediate release of insulin evoked by either secretagogue to the sustained release of insulin.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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