Interacting Effects of Sulfonylureas and Glucose on Cyclic AMP Metabolism and Insulin Release in Pancreatic Islets of the Rat

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Abstract

The effects of tolbutamide and glibenclamide on the metabolism of cyclic AMP were investigated in pancreatic islets of the rat. Changes in cyclic AMP were assessed by measuring [3H]cyclic AMP after labeling of the islets with [2-3H]adenine. In the presence of a nonstimulatory concentration of glucose (3.3 mM), both sulfonylureas caused a rapid increase in islet [3H]cyclic AMP, which declined within 5 (tolbutamide) or 10 min (glibenclamide). In the absence of glucose, the glibenclamide effect was shortened, but the initial (1 min) response of [3H]-cyclic AMP was unaffected. Glucose could be substituted with d-glyceraldehyde but not pyruvate for prolongation of the glibenclamide response. The effect of glucose withdrawal on the glibenclamide response was reproduced by the addition of d-mannoheptulose to glucose containing media.

Authors

V. Grill, E. Cerasi