Effects of a High Fat Diet and Electric Stress on Adenylate Cyclase Activity and Insulin Release in Isolated Islets of Langerhans

Abstract

The effects of glucose, glucagon and epinephrine on adenylate cyclase activity in homogenates of isolated islets and insulin release were studied in rats fed on either a control or a high fat diet for 12 weeks. Rats were divided into non-stress group and stress group. Rats in stress groups received electrical shocks (1 hr/day) for the last 3 weeks of the experimental period. Islet adenylate cyclase activity was measured by the conversion of [2-³H]ATP to cyclic [³H]AMP. While the basal activity of adenylate cyclase was increased by stress, it was reduced by the high fat diet. In the presence of a low glucose concentration, the adenylate cyclase activity was higher in non-stress groups rather than in stress groups. However, the adenylate cyclase activity was not altered by an increase in glucose concentration. Characteristically, the adenylate cyclase activity in fat diet-stress group was reduced by 16.7 mM glucose and glucose-stimulated insulin release was low. Stress enhanced glucagon-stimulated adenylate cyclase activity, which was reduced by the high fat diet. The effect of glucagon on adenylate cyclase activity was similar to that on insulin release. Epinephrine (10^-6M) did not alter the adenylate cyclase activity in all four groups. It is concluded that a decrease of glucose-stimulated insulin release produced by the combined actions of a high fat diet and electric stress may involve at least partly the inhibition of adenylate cyclase-cyclic AMP system activated by glucose itself.