Hepatic lipid metabolism in experimental diabetes: III. Synthesis and utilization of triglycerides.

Livers removed from normal rats, from alloxan diabetic rats maintained on insulin for two weeks (ADI+), and from insulin-treated diabetic rats from which insulin had been withdrawn two days before use (AD) were perfused in vitro with 120 mg (468 mumoles) palmitic acid-1-C(14). Under these conditions, output of TG (triglyceride) was depressed in livers from ADI+ rats and was negligible with livers from AD animals. The total incorporation of C(14) into perfusate TG paralleled the chemical measurments of TG output. The concentration of hepatic TG increased during perfusion of livers from normal or ADI+ rats but decreased during perfusion of livers from AD animals.A load of 120 mg of palmitic acid/3 hr was inadequate to maintain net accumulation of TG in livers from AD rats; furthermore it is implicit in this observation that the total load of NEFA (nonesterified fatty acid) perfusing livers from AD rats must be increased considerably to obtain a fatty liver. The total incorporation of C(14) into hepatic TG and the specific activity of hepatic TG were depressed during perfusion of livers from AD rats. The production of ketone bodies by livers from AD animals was about five times the normal rates; the output of ketone bodies did not differ from results of other experiments (1) in which the load of palmitic acid added to the medium was varied from 0-80 mg. These observations were discussed with reference to mechanisms for ketogenesis and fatty liver in alloxan diabetes.