Inhibitory action of the anomers of 2-deoxy-D-glucose tetraacetate on the metabolism of D-glucose in rat pancreatic islets.

Abstract

The tetra-acetate ester of 2-deoxy-D-glucose was recently found to either inhibit or augment insulin secretion, depending on the concentration of the ester. Both the positive and negative insulinotropic actions of the ester display anomeric specificity. The effects of the alpha- and beta-anomer of 2-deoxy-D-glucose tetra-acetate (5.0 mM) on the metabolism of D-[5-3H]glucose and D-[U-14C]glucose (8.3 mM) were investigated in isolated rat pancreatic islets. Both the alpha- and beta-anomers of 2-deoxy-D-glucose tetra-acetate inhibited the generation of 3HOH from D-[5-3H]glucose and that of 14CO2, as well as radioactive acidic metabolites and amino acids, from D-[U-14C]glucose. They also lowered the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization. No significant anomeric difference could be detected, however, in these experiments. The effects of the alpha- and beta-anomer of 2-deoxy-D-glucose tetra-acetate on the metabolism of D-glucose in isolated rat pancreatic islets reinforce the view that the insulinotropic action of monosaccharide esters involves a dual mode of action, linked to both the metabolic effects of their glucidic moiety and a direct interaction of the esters themselves with a stereospecific receptor system.