Abstract
Epinephrine-induced changes in insulin release and cyclic AMP levels were measured simultaneously in isolated rat islets. Forskolin was used to enhance islet cyclic AMP levels. Forskolin (30 microM) stimulated adenylate cyclase activity 10-fold in islet homogenates and raised cyclic AMP levels 5-fold in intact islets (both at low and high glucose). Insulin release was enhanced by forskolin only at high glucose. Epinephrine (0.1 microM) inhibited glucose- and forskolin-induced insulin release to basal rates. At the same time epinephrine potentiated forskolin-elevated cyclic AMP levels. In contrast epinephrine attenuated forskolin-stimulated adenylate cyclase activity in islet homogenates. At low glucose, both alpha 2- and beta-adrenergic blockade counteracted the epinephrine potentiation, each by 50%. At high glucose the effect was mainly beta-adrenergic in nature. The actions of epinephrine in the presence of a beta-blocker were mimicked by the alpha 2-agonist clonidine. Despite the variations in cyclic AMP levels stimulated insulin release was always inhibited by activation of alpha 2-receptors. Finally, insulin release stimulated by exogenous cyclic AMP was abolished by epinephrine. These results suggest that epinephrine inhibits insulin release at a step distal to the generation of cyclic AMP.
Highlights
Epinephrine-induced changes in insulin release and lowering of cyclic AMP levels depended on the presence of cyclic AMP levels weremeasuredsimultaneouslyin phosphodiesterase inhibitors (6, 8, 9), as no effect was seen isolated ratislets
Our results reveal a clear dissociation between the effects of epinephrine on islet cyclic AMP levelsand insulin release, in that forskolin-enhanced islet cyclic AMP was further augnature
Despite the variationisn cyclic AMP levels stimulated of 8-bromo-cyclic AMP, epinephrine inhibited the stiminsulin release was always inhibited by activation of ulation of release
Summary
These results suggest that epinephrine inhibits insulin Islet Isolation and Incubation-Pancreatic islets were isolated by release at a step distal to the generatiocnycolfic AMP. the collagenase technique from male Wistar rats (15). These results suggest that epinephrine inhibits insulin Islet Isolation and Incubation-Pancreatic islets were isolated by release at a step distal to the generatiocnycolfic AMP. Measurements of Adenylate CyckzseActivity inIslet Homogenatesmeasurement of insulin release It appears that epinephrine Homogenates from freshly isolated rat islets were prepared as described by Katada and Ui (5) with the following modifications. Clonidine production was terminatedby the addition of[10] pl of 0.33 M ZnSO, and 10 pl of 0.5 M Na2COs. 20 pl of the finalsupernatant was transferred to a glass tube, and[80] pl of 0.05M acetate buffer,pH 6.2, were added These 100-pl samples were succinylated for the cyclic did not affect islet cyclic AMP raised by forskolin. A-Yohimbine abolished the inhibitory action of epinephrine on forskolin-stimulated insulin release but had no effect of its own (Table IA). Propranolol (10 p ~ )w,hich did not alter the effect of forskolin on islet cyclicAMP at low and highglucose, inhibited the potentiating effect of epinephrine by 56% at 2
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
