Insulinotropic action of the polyacetate esters of two non-nutrient monosaccharides in normal and diabetic rats.

The polyacetate esters of certain non-nutrient monosaccharides, such as L-glucose and 2-deoxy-D-glucose, were recently reported to display positive insulinotropic action and, hence, proposed as possible tools for stimulation of insulin release in non-insulin-dependent diabetes. In the present study, the secretory response to four carbohydrate esters was compared in islets of both normal and hereditary diabetic Goto-Kakizaki rats. Three major findings are documented. First, in islets exposed to the dimethyl ester of succinic acid (10.0 mmol/l), D-mannoheptulose hexaacetate (1.7 mmol/l) was found to stimulate insulin release in both normal and diabetic rats. Second, relative to the control value recorded in the sole presence of the succinic acid ester, the increments in insulin output evoked by D-mannoheptulose hexaacetate, alpha-L-glucose pentaacetate and beta-D-glucose pentaacetate (all 1.7 mmol/l) were not lower and, on occasion, even higher in diabetic rats than in control animals. Last, the sole exception to such a rule was encountered in islets exposed to beta-L-glucose pentaacetate, in which case the hexose moiety of the ester might mimic the inhibitory effect of alpha-D-glucopyranose upon phosphorylase a-catalyzed glycogenolysis in islets from diabetic rats. These findings reinforce the concept that the insulinotropic action of monosaccharide esters is not solely attributable to the catabolism of their carbohydrate moiety but also to a direct effect of the esters themselves upon a yet unidentified receptor system. They also provide further support to the possible use of the esters of non-nutrient monosaccharides as insulinotropic tools in type-2 diabetes.