AJP - Endocrinology and Metabolism, Vol 247, Issue 6 701-E708, Copyright © 1984 by American Physiological Society
Mechanisms of synergism between glucose and cAMP on stimulation of insulin release
W. Phang, L. Domboski, Y. Krausz and G. W. Sharp
The mechanism of synergism between glucose and adenosine 3',5'-cyclic
monophosphate (cAMP) on insulin release has been studied. Synergism may
result from 1) inhibition of Na+-Ca2+ exchange by glucose and 2) a
cAMP-induced sensitization of the release machinery to Ca2+. To distinguish
between these two possibilities, isolated rat pancreatic islets were
perifused with agents that raise intracellular levels of cAMP
[3-isobutyl-1-methylxanthine (IBMX) and forskolin] and others that increase
intracellular concentrations of Ca2+ either by blocking Na2+-Ca2+ exchange
(ouabain and choline-Ringer solution) or by causing increased Ca2+ influx
(KCl, carbachol, and 10 mM Ca2+). The results indicate that both the
combination of cAMP and increased Ca2+ influx or blocked Na2-Ca2+ exchange
and increased Ca2+ influx potentiated insulin release. When the relative
potentiating abilities of cAMP and blocked Na2+-Ca2+ exchange were compared
by determining the individual effects of IBMX and 1 mM ouabain (a
concentration that causes similar inhibition of 45C2+ efflux as 16.7 mM
glucose) in the presence of carbachol, cAMP was only 1.4 times more potent
as a potentiating agent than blocked Na+-Ca2+ exchange. The greatest
potentiation of insulin release was observed when Na+-Ca2+ exchange was
blocked in the presence of increased levels of intracellular cAMP.
