AJP - Endocrinology and Metabolism, Vol 239, Issue 2 132-E138, Copyright © 1980 by American Physiological Society
Role of Ca2+ in impaired insulin release from islets of diabetic (C57BL/KsJ-db/db) mice
E. G. Siegel, C. B. Wollheim, G. W. Sharp, L. Herberg and A. E. Renold
The involvement of Ca2+ in the impaired insulin release of diabetic
C57BL/KsJ-db/db mice was studied. Twenty-week-old severely hyperglycemic
mice were compared to nondiabetic C57BL/KsJ mice as controls.
Collagenase-isolated islets were maintained for 46 h in tissue culture
allowing for equilibration at the same glucose concentration (8.3) mM). The
insulin content of both types of islets was similar. In control islets
preloaded during culture with 45Ca2+ glucose-induced insulin release was
associated with increased 45Ca2+ effux. Islets from diabetic mice showed
markedly reduced insulin response to glucose and a smaller increase in
45Ca2+ efflux. Because insulin release was strikingly potentiated by
3-isobutyl-1-methylxanthine (IBMX), even more than in control islets, there
was no generalized release defect. In both types of islets, IBMX
potentiation was accompanied by a further enhanced 45Ca2+ efflux, possibly
suggesting that cAMP effects are associated with increased cytosol Ca2+%
concentrations. As Ca2+ uptake was stimulated by glucose in both types of
islets, a defect may lie in the mechanism by which glucose uses cellulr
calcium to raise cytosol Ca2+ in the beta-cell of these diabetic mice.
