Insulinotropic action of alpha-D-glucose pentaacetate: metabolic aspects

Abstract

The metabolism and metabolic effects of alpha-D-glucose pentaacetate were investigated in isolated rat pancreatic islets. Several findings were compatible with the view that the insulinotropic action of alpha-D-glucose pentaacetate is causally related to its capacity to act as a fuel in the islet B-cell. First, the ester was efficiently taken up and hydrolyzed with resulting accumulation of D-glucose in the islet cells. Second, the conversion of alpha-D-[5-3H]glucose pentaacetate to 3HOH and that of alpha-D-[U-14C]glucose pentaacetate to 14CO2 exceeded those found at an equimolar concentration (1.7 mM) of D-glucose and were both inhibited by 2-deoxy-D-glucose (16.7 mM). Last, the ester inhibited the catabolism of both exogenous D-glucose or endogenous fatty acids. Yet, an apparent dissociation between the metabolic and secretory responses to the ester was suggested by the failure of alpha-D-glucose pentaacetate to increase O2 uptake by the islets. Moreover, there were striking differences between the catabolism of the ester and that of unesterified D-glucose, such as a much higher intracellular D-glucose content and an insensitiveness to the inhibitory action of D-mannoheptulose in islets exposed to alpha-D-glucose pentaacetate. Likewise, the ratio between hexose oxidation and utilization was lower for alpha-D-glucose pentaacetate than for unesterified D-glucose in islets concomitantly exposed to the hexose and its ester. It is proposed, therefore, that the insulinotropic action of alpha-D-glucose pentaacetate, although probably linked to the intracellular generation of D-glucose from the ester, may not involve the same coupling process between metabolic and functional events as that currently implied in the process of glucose-stimulated insulin release.