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.
Cancelas
J
J
Fundacion Jimenez Diaz, Madrid, Spain.
Acitores
A
A
Villanueva-Penacarrillo
M L
ML
Malaisse
W J
WJ
Valverde
I
I
D000818:Animals; D002469:Cell Separation; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004789:Enzyme Activation; D005947:Glucose / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006006:Glycogen Synthase / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
C105128:glucose pentaacetate; D019344:Lactic Acid; D006006:Glycogen Synthase; D005947:Glucose