ARTICLES

Regulation of hepatic free fatty acid metabolism by glucagon and insulin

The roles of glucagon and insulin in the direct short-term regulation of hepatic free fatty acid (FFA) metabolism were studied in hepatocytes isolated from fed, fasted, and streptozotocin-induced diabetic rats. In fed animals, the principal metabolic product of palmitate metabolism was triglyceride, whereas ketones were the major product in fasted and diabetic animals. Glucagon at physiological concentrations increased ketogenesis and decreased triglyceride synthesis from palmitate in hepatocytes from fed rats at FFA concentrations 1.0 mM or less. Insulin had no effect on FFA metabolism when present as the sole hormone, but could antagonize the actions of submaximal concentrations of glucagon. The metabolism of palmitate in fasted or diabetic hepatocytes was unaffected by either hormone. Ketogenesis from octanoate was also unaffected by hormone addition in all cell types. These data are consistent with a locus of hormonal regulation at a step prior to beta-oxidation of fatty acid. Glucagon and insulin may modulate FFA metabolism by both intrahepatic and extrahepatic mechanisms.