Extracellular calcium and adrenergic and cholinergic effects on islet beta-cell function

Abstract

An in vitro perifusion system utilizing collagen-medium calcium on the dynamics of insulin release as induced by acetylcholine (ACh) stimulation (in the presence of glucose, 2.4 mM) and as modified by prior perfusion of islets in epinephrine. Continuous challenge with ACh produces a biphasic insulin release response, both phases of which are reduced when the medium calcium concentration is reduced during stimulation; when the calcium content is reduced during an initial perifusion period of 30 min and then replaced during subsequent stimulation only the first phase of the response to ACh is affected; perifusion with epinephrine prior to stimulation with ACh produces enhancement of both phases of ACh-induced insulin release when calcium in both media is normal. However,.when this experiment is repeated utilizing a medium with low calcium content during the period of exposure to epinephrine the priming effect of epinephrine on the subsequent insulin response to ACh is abolished (in fact, reversed). These studies provide direct evidence for a role for calcium in mediating an effect of epinephrine on insulin release. Further, the data suggest that epinephrine affects Ca transport in islets in some manner beyond stimulating net efflux from islets, perhaps by enhancing membrane binding of calcium.