Studies of the mechanism of action of 3′, 5′-cyclic nucleotides on hepatic glucose production

Abstract

In order to elucidate the mechanism of action of 3′5′ cyclic nucleotide-induced hepatic glucose production, isolated rat livers were perfused with a variety of cyclic nucleotides. Hepatic levels of cyclic AMP, which were increased 2 to 3 fold by glucagon perfusion, did not exceed control levels (1.12±20 picomoles/g) after perfusion with cyclic GMP or cyclic IMP, which were equipotent to cyclic AMP in stimulating glucose production, or with pyrimidine 3′5′ cyclic nucleotides (cyclic UMP, cyclic CMP, cyclic TMP), which were less potent. Measurement of the glycolytic intermediates demonstrated that cyclic GMP and cyclic IMP, like glucagon and cyclic AMP, induced a characteristic gluconeogenic stimulation of the pyruvate to phosphoenolpyruvate sequence. Pyrimidine cyclic nucleotides induced non-specific patterns of glycolytic intermediary metabolism.