Effects of Insulin and Fatty Acids on Gluconeogenesis in the Rat

Abstract

The present study was undertaken to examine the mechanism of insulin action on gluconeogenesis in the rat. Conversion of pyruvate to glucose was estimated by measuring the radioactivity of the blood glucose and liver glycogen at short intervals, usually between 5 min and 1 hour, after injection of pyruvate-3-14C. In alloxan-diabetic rats insulin at high dosage markedly lowered incorporation of pyruvate-3-14C into blood glucose, but also stimulated its incorporation into liver glycogen. However, total incorporation into blood glucose and liver glycogen was decreased by insulin. When insulin was withdrawn from insulin-treated, alloxan-diabetic rats, the incorporation rose gradually over 3 days to the untreated diabetic level. Insulin lowered the incorporation of pyruvate-3-14C into blood glucose of fasted or fat-fed rats, and also lowered incorporation in liver glycogen. Octanoate injected intraperitoneally into normal, carbohydrate-fed rats markedly enhanced pyruvate-3-14C incorporation into blood glucose. This effect was accompanied by lowered liver glycogen and increased blood glucose levels, but was without effect on the incorporation of pyruvate-3-14C into liver glycogen. On the basis of present knowledge of insulin action, taken in conjunction with known effects of long chain acyl coenzyme A esters and acetyl-CoA on intermediary metabolic reactions in liver, these results suggest that the high hepatic gluconeogenesis of fasting and diabetes is promoted by high hepatic acyl-CoA levels, and that the prompt and marked suppression of hepatic gluconeogenesis by insulin is due to its antilipolytic action on adipose tissue.