Activation of glycogen synthase a in hepatocytes exposed to alpha-D-glucose pentaacetate.

The effects of alpha-D-glucose pentaacetate (1.7 mM) upon glycogen synthase a activity and lactate output were examined in rat hepatocytes incubated at increasing concentrations of D-glucose. The ester enhanced the activity of glycogen synthase a at all concentrations (2.8, 4.0 and 8.0 mM) of D-glucose, which itself provoked a concentration-related increase in enzymatic activity. Likewise, the output of lactate augmented at increasing concentrations of D-glucose. However, alpha-D-glucose pentaacetate failed to cause a further increase in lactate output, the trend being even towards a lower production of lactate in the presence than absence of the ester. These findings suggest that the activation of glycogen synthase a by alpha-D-glucose pentaacetate and the subsequent increase in glycogen synthesis are sufficiently pronounced to prevent the increase in glycolysis otherwise expected from the generation of unesterified D-glucose from the same ester. Such a situation, which differs from that previously documented in pancreatic islet cells, could be favourable in the perspective of using alpha-D-glucose pentaacetate as a novel insulinotropic, and hence hypoglycaemic, tool in the treatment of non-insulin-dependent diabetes mellitus.