INSULINOTROPIC ACTION OF THE POLYACETATE ESTERS OF 2 NONNUTRIENT MONOSACCHARIDES IN NORMAL AND DIABETIC RATS

The polyacetate esters of certain non-nutrient monosaccharides, such a s L-glucose and 2-deoxy-D-glucose, were recently-reported to display p ositive insulinotropic action and, hence, proposed as possible fools f or stimulation of insulin release in non-insulin-dependent diabetes. I n the present study, the secretory response to four carbohydrate ester s was compared in islets of both normal and hereditary diabetic Goto-K akizaki rats. Three major findings are documented. First, in islets ex posed to the dimethyl ester of succinic acid (10.0 mmol/l), D-mannohep tulose hexaacetate (1.7 mmol/l) was found to stimulate insulin release in both normal and diabetic rats. Second, relative to the control val ue recorded in the sole presence of the succinic acid eater, the incre ments in insulin output evoked by D-mannoheptulose hexaacetate, alpha- 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 encounter ed in islets exposed to beta-L-glucose pentaacetate, in which case the hexose moiety of the eater might mimic the inhibitory effect of alpha -D-glucopyranose upon phosphorylase alpha-catalyzed glycogenolysis in islets from diabetic rats. These findings reinforce the concept that t he insulinotropic action of monosaccharide esters is not solely attrib utable to the catabolism of their carbohydrate moiety but also to a di rect effect of the esters themselves upon a yet unidentified receptor system. They also provide further support to the possible use of the e sters of non-nutrient monosaccharides as insulinotropic tools in type- 2 diabetes.