Effects of tetracaine on insulin release and calcium handling by rat pancreatic islets

Abstract

The effects of tetracaine on insulin release and 45Ca2+ handling by rat pancreatic islets have been studied under basal (2.8 mM glucose), glucose-stimulated (5.6, 8.3, and 16.7 mM glucose), and 3-isobutyl-1-methylxanthine (IBMX)-stimulated conditions. Islets were isolated by the use of collagenase and used either directly (freshly isolated islets) or after a period under tissue culture conditions. Tetracaine was found to stimulate insulin release under basal conditions, to inhibit glucose-stimulated insulin release, and to potentiate insulin release stimulated by IBMX. In studies on the mechanisms underlying these effects, tetracaine was found to decrease glucose-stimulated net retention of 45Ca2+ (by an action to block the voltage-dependent Ca channels) and to mobilize Ca2+ from intracellular stores. These two actions form the basis for the inhibition of glucose-stimulated insulin release, which depends heavily on Ca2+ entry via the voltage-dependent channels and the synergism with IBMX to potentiate release. No inhibition of IBMX-stimulated release occurs because IBMX does not use the voltage-dependent channels to raise intracellular Ca2+.