The Roles of Intracellular and Extracellular Ca⁺⁺ in Glucose-Stimulated Biphasic Insulin Release by Rat Islets

• Text
• PDF

Abstract

Verapamil, an agent known rapidly to block calcium uptake into islets of Langerhans, has been used to study the roles of intra- and extracellular calcium in the two phases of glucose-induced insulin release. Rates of calcium uptake and insulin release during the first phase were measured simultaneously over 5 min in rat islets after maintenance in tissue culture for 2 days. Rates of 45Ca++ efflux and insulin release during the first and second phases were also measured simultaneously under perifusion conditions. For this, islets were loaded with 45Ca++ during the entire maintenance period to complete isotopic equilibrium. Under static incubation conditions 5 μM Verapamil had no effect upon Ca++ uptake or insulin release in the presence of 2.8 mM glucose. By contrast, glucose-stimulated calcium influx was totally abolished without there being any significant effect upon first phase insulin release. Thus first phase insulin release is independent of increased uptake of extracellular calcium. The lack of effect of 5 μM Verapamil blockade on first phase insulin release was confirmed, under perifusion conditions, and was in marked contrast to the observed 55% inhibition of second phase release. 45Ca++ efflux was inhibited during both phases of the insulin release response.

Authors

Claes B. Wollheim, Masatoshi Kikuchi, Albert E. Renold, Geoffrey W. G. Sharp