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 a t increasing concentrations of D-glucose. The ester enhanced the activity o f glycogen synthase a at all concentrations (2.8, 4.0 and 8.0 mM) of D-gluc ose, which itself provoked a concentration-related increase in enzymatic ac tivity. Likewise, the output of lactate augmented at increasing concentrati ons of D-glucose. However, alpha-D-glucose pentaacetate failed to cause a f urther increase in lactate output, the trend being even towards a lower pro duction of lactate in the presence than absence of the ester. These finding s suggest that the activation of glycogen synthase a by alpha-D-glucose pen taacetate and the subsequent increase in glycogen synthesis are sufficientl y pronounced to prevent the increase in glycolysis otherwise expected from the generation of unesterified D-glucose from the same eater. Such a situat ion, which differs from that previously documented in pancreatic islet cell s, could be favourable in the perspective of using alpha-D-glucose pentaace tate as a novel insulinotropic, and hence hypoglycaemic, tool in the treatm ent of non-insulin-dependent diabetes mellitus.