Regulation of fatty acid and carbohydrate metabolism by insulin, growth hormone and tri-iodothyronine in hepatocyte cultures from normal and hypophysectomized rats

Abstract

The interactions of insulin, growth hormone (somatotropin) and tri-iodothyronine (T3) in the long-term (24 h) regulation of fatty acid and carbohydrate metabolism were studied in hepatocyte primary cultures isolated from normal or hypophysectomized Sprague-Dawley rats. Hepatocytes from hypophysectomized rats had similar rates of palmitate metabolism, but lower rates of ketogenesis, than hepatocytes from normal rats. They also had a lower endogenous triacylglycerol content and lower activities of NADP-linked dehydrogenases than did cells from normal rats. The inhibitions of ketogenesis and gluconeogenesis by insulin were more marked in hepatocytes from hypophysectomized than from normal rats. Insulin caused a 7-10-fold increase in cellular glycogen in hepatocytes from hypophysectomized rats, compared with a 2-3-fold increase in cells from normal rats, and it increased cellular triacylglycerol by 65% in cells from hypophysectomized rats, compared with 11% in cells from normal rats. In hepatocytes from hypophysectomized rats, growth hormone and T3 increased ketogenesis both separately and in combination (12% and 23% respectively; P less than 0.05), whereas in hepatocytes from normal rats only the combination of growth hormone and T3 caused a significant increase in ketogenesis. In cells from hypophysectomized rats, T3 and growth hormone had different effects on carbohydrate metabolism: T3, but not growth hormone, potentiated the anti-gluconeogenic and glycogenic effects of insulin. It is concluded that hypophysectomy increases the responsiveness of hepatocytes to insulin, growth hormone and T3, and that growth hormone and T3 regulate fatty acid and carbohydrate metabolism by different mechanisms.