Hepatic Lipid Metabolism in Experimental Diabetes: IV. Incorporation of Amino Acid 14C Into Lipoprotein-Protein and Triglyceride

Abstract

Abstract The incorporation of radioactive amino acids into serum proteins by isolated perfused livers from alloxan diabetic rats was depressed in comparison to the normal. The incorporation of amino acids into the major classes of serum lipoproteins (density l1.020; density 1.020 to 1.063; density 1.063 to 1.210) also was impaired in alloxan diabetes. The incorporation of 14C into the total serum proteins and into the lipoproteins was also depressed with livers from chronic alloxan diabetic rats maintained on insulin, and was not further depressed after withdrawal of the insulin from the animals. The incorporation of amino acids into serum proteins was not restored to normal levels upon treatment of the diabetic rats with insulin under our experimental conditions. The incorporation of amino acids into hepatic protein also appeared to be depressed below normal in livers from diabetic rats. The conversion of amino acid 14C to fatty acid carbon of liver and serum triglycerides was reduced with perfused livers from acute and chronic alloxan diabetic rats and was stimulated when the animals were treated with insulin. In diabetes, an increase in the incorporation of amino acid 14C into glyceride-glycerol and into water-soluble neutral compounds of the perfusate was observed, and production of urea and output of amino acid nitrogen were also elevated. The inhibition of synthesis and, possibly, release of the protein moiety of the density l1.020 serum lipoprotein (the carrier of the major proportion of the serum triglyceride) which was observed in perfused livers from acute and chronic alloxan diabetic rats may not be causally related to the inhibition of release of triglyceride in diabetes, since, upon administration of insulin to the diabetic animal, the release of triglyceride by the liver was stimulated even though the defect in the synthesis of serum lipoprotein-protein persisted.