Some Metabolic Effects of Phenformin in Rat Adipose Tissue

Abstract

In rat adipose tissue, phenformin (5 × 10−4M) inhibited the oxidation of C1 and C6 of glucose to CO2, blocked the stimulatory effect of insulin (32 μU./ml.) on Ct oxidation, inhibited lipogenesis from C1 and C6 of glucose, and abolished the stimulatory effect of acetate on glucose oxidation and lipogenesis. These effects were accompanied by lactate accumulation. Such inhibitory effects suggest that phenformin interrupts the pentose shunt and lipogenesis, both of which are pyridine nucleotide-linked processes. Phenformin was shown, by inhibition of oxidation of pyruvate C1, to interfere with the sequence at the point of pyruvate decarboxylation, since acetate incorporation was not affected. Both pyruvate decarboxylation and oxidation of acetate in the tricarboxylic acid cycle were blocked, presumably by interference with electron transport. This effect of phenformin on pyruvate decarboxylation is sufficient to explain the observed reduction in pentose shunt activity and lipogenesis as well as the increased lactate accumulation.