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Mode of action of hypoglycemic agents. V. Studies with phenethylbiguanide in isolated perfused rat liver.

Abstract In isolated perfused rat liver, phenethylbiguanide inhibits the rate of glucose production from both lactate and dihydroxyacetone, but not from xylitol. With all substrates studied, phenethylbiguanide decreases the steady state concentrations of fructose 6-phosphate and α-ketoglutarate, decreases the ATP:ADP ratio, decreases citric acid cycle activity, and causes both the mitochondrial and cytosolic oxidation-reduction states to be more reduced. The results presented and discussed are interpreted to indicate that phenethylbiguanide influences hepatic gluconeogenesis by an indirect mechanism.