AJP - Endocrinology and Metabolism, Vol 273, Issue 1 E52-E58, Copyright © 1997 by American Physiological Society
Modulation of gliquidone action by forskolin in the pancreas of normal and GK rats
V. Leclercq-Meyer and W. J. Malaisse
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
This study aims to investigate whether agents that stimulate adenosine
3',5'-cyclic monophosphate (cAMP) formation could be used to increase
insulin release evoked by hypoglycemic sulfonylureas in
non-insulin-dependent diabetes mellitus. For this purpose, the effect of
gliquidone (1.0 microM) on insulin and glucagon release was examined in the
perfused pancreas of either normal or Goto-Kakizaki (GK) rats at a low
concentration of D-glucose (2.8 mM) and in the absence or presence of
forskolin (1.3 microM). In normal rats, the diterpene exerted relatively
little effect on basal insulin release but markedly augmented the
insulinotropic action of gliquidone. In GK rats, forskolin dramatically
augmented both basal and gliquidone-stimulated insulin output. In mirror
image of its effect on insulin release, forskolin augmented basal glucagon
output and failed to increase the secretory response of the A cell to
gliquidone, at least in normal rats. On the contrary, in GK rats,
forskolin, while slightly enhancing basal glucagon output, unmasked the
glucagonotropic potential of gliquidone that was otherwise not detected in
the diabetic animals. These findings are interpreted in light of a dual
metabolic and energy-independent response of islet cells to the
forskolin-induced generation of cAMP. They document the optimalization by
endogenous cAMP of the B cell secretory response to gliquidone in
non-insulin-dependent diabetes.
