Early Effects of Anti-Insulin Serum on Hepatic Metabolism of Plasma Free Fatty Acids in Dogs

SUMMARY:Hepatic metabolism of free fatty acids was studied in six anesthetized fasted dogs before and for several hours after the abrupt induction of insulin deficiency. This was produced by injecting guinea pig anti-insulin serum in amounts capable of binding all circulating insulin for several hours. During each study, albumin-bound-I-C-14-palmitate and I-131-rose bengal were infused at a constant rate and serial sanv pies of arterial, portal and hepatic venous blood were obtained through appropriate intravascular catheters. Maximal changes were observed three to four hours after administration of anti-insulin serum. Mean arterial concentrations of glucose, free fatty acids, glycerol and triglyceride fatty acids of very low density lipoproteins increased twofold and that of ketone bodies, fourfold. Hepatic extraction ratio of free fatty acids was unchanged after anti-insulin serum so that the hepatic uptake of free fatty acids approximately doubled. During the control period, about 25 per cent of free fatty acids removed by the liver were converted to CO2, 11 per cent to triglyceride fatty acids of very low density lipoproteins and 25 per cent to ketones (assuming that ketones derived entirely from FFA). After anti-insulin serum, corresponding values were 14 per cent, 26 per cent and 51 per cent. The increased relative and absolute conversion of free fatty acids to ketones resembles that observed in chronically diabetic dogs withdrawn from insulin for forty-eight hours. However, the increased conversion of free fatty acids to triglyceride fatty acids of very low density lipoproteins observed in short-term deficiency of insulin contrasts with the greatly depressed conversion observed after two days of insulin lack.