Hydrazonopropionic acids, a new class of hypoglycemic substances. 5. Inhibition of hepatic gluconeogenesis by 2-(3-methylcinnamyl-hydrazono)-propionate in the rat and guinea pig.

2-(3-Methyl-cinnamyl-hydrazono)-propionate (MCHP) is a new compound which effectively lowers the blood glucose level in guinea pigs. 0.04 mmol/l MCHP inhibited glucose formation from lactate, pyruvate and alanine, but not from dihydroxyacetone in the perfused guinea pig liver. In the presence of both hexanoic acid and alanine, 0.04 mmol/l MCHP did not effect hepatic gluconeogenesis. Gluconeogenesis was probably reduced by an inhibition of the pyruvate carboxylase: The pattern of hepatic metabolite concentrations indicated a block between pyruvate and the triose phosphates. The intrahepatic concentration of acetyl-CoA was consistently decreased. The decrease of the acetyl-CoA concentration could be explained by an influence of MCHP on the fatty acid oxidations, which occurred at the carnitine palmitoyl transferase (CPT) step. This hypothesis is supported by the fact that a medium chain fatty acid not requiring CPT reversed the inhibition of gluconeogenesis by MCHP. From all results reported it is concluded that transamination and oxidative phosphorylation were not effected to a degree relevant for the inhibition of gluconeogenesis by 0.04 mmol/l MCHP.