Effects of D-mannoheptulose and its hexaacetate ester upon D-glucose metabolism in rat hepatocytes.
D-mannoheptulose, which inhibits hexokinase isoenzymes in a predominantly competitive manner, has been found to decrease much more modestly D-glucose metabolism in pancreatic islets exposed to a low, as distinct from high, concentration of the hexose. In the present study, which aimed at investigating the factor(s) possibly responsible for such a phenomenon, a comparable situation was found to prevail in rat hepatocytes. However, when the hexaacetate ester of D-mannoheptulose was used instead of the unesterified heptose, the relative extent of inhibition of D-[5-3H]glucose utilization and D-[U-14C]glucose conversion to 14C-labelled acidic metabolites was comparable in hepatocytes exposed to either 1.7 or 8.3 mM D-glucose. Moreover, at the low D-glucose level, the incorporation of 3-O-methyl-D-glucose (6.6 mM) into the incubation medium increased the inhibitory action of unesterified D-mannoheptulose upon D-glucose metabolism. These findings suggest that an insufficient uptake of the heptose accounts, in part at least, for its poor efficiency as inhibitor of D-glucose catabolism in liver, and presumably islet cells exposed to low concentrations of the hexose.
Ladriere
L
L
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Kadiata
M M
MM
Malaisse
W J
WJ
D019325:3-O-Methylglucose / Q000494:pharmacology; D000085:Acetates / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004952:Esters; D005260:Female; D005947:Glucose / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008356:Mannoheptulose / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D004952:Esters; D019325:3-O-Methylglucose; D008356:Mannoheptulose; D005947:Glucose