COMPARISON OF THE EFFECTS OF D-MANNOHEPTULOSE AND ITS HEXAACETATE ESTER ON D-GLUCOSE METABOLISM AND INSULINOTROPIC ACTION IN RAT PANCREATIC-ISLETS

It was recently, and surprisingly, found that D-mannoheptulose did not affect D-glucose metabolism and insulinotropic action in pancreatic i slets incubated at a low concentration of D-glucose. To explain this f inding, the metabolism and secretory response to the hexose were inves tigated in rat islets exposed to D-mannoheptulose hexaacetate, which w as recently found to inhibit D-glucose catabolism in cells that are ot herwise fully resistant to the heptose, At a high concentration of D-g lucose (16.7 mmol/l), the utilisation of D-[5-H-3]glucose and oxidatio n of D-[U-C-14]glucose, as well as the insulinotropic action of the he xose, were affected less by D-mannoheptulose tetraacetate than by unes terified D-mannoheptulose. This coincided with a reduced uptake of the ester by intact islets and a lower rate of hydrolysis of the ester in islet homogenates compared with findings in other monosaccharide este rs such as D-glucose pentaacetate, At a low concentration of D-glucose (2.8 mmol/l), D-mannoheptulose hexaacetate was slightly more efficien t than the unesterified heptose in reducing D-glucose catabolism, but still failed to suppress the secretory response to the hexose. These f indings do not necessarily mean that unesterified D-mannoheptulose ent ers beta-cells more efficiently at high than at low extracellular D-gl ucose concentrations, especially if possible differences in the respec tive contributions of distinct islet cell types to the overall catabol ism of D-glucose by whole islets is allowed for. These data do not rul e out the possibility that D-glucose phosphorylation is more resistant to D-mannoheptulose in beta cells incubated at a low than a high conc entration, independently of any difference in the intracellular concen tration of the heptose. However, the mechanism of this resistance is s till not explained.