Studies on the Relationship Between Glucose Oxidation and Intermediary Metabolism. II. The Role of Glucose Oxidation in Lipogenesis in Diabetic Rat Liver12

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Abstract
A study of the nature of the lipogenic defect in the diabetic liver was undertaken using cell-free preparations of livers from alloxan-diabetic rats. By the addition of glucose-6-phosphate and either diphosphopyridine nucleotide or triphosphopyridine nucleotide glycolysis was restored in the diabetic liver respectively over the Embden-Meyerhof or hexosemonophosphate (HMP) pathways. The effect of repairing each of these pathways on the incorporation of acetate-C14 into fatty acids and cholesterol was then studied. It was concluded that the lipogenic lesion in diabetes is due primarily to a deficiency of glucose oxidation via the hexosemonophosphate pathway; the depressed glycolysis over the Embden-Meyerhof route, which also accompanies the diabetic state, apparently plays a minor role in blocking lipogenesis. Since an alternate TPNH generating system will also repair the lipogenic defect of diabetes, it is concluded that a deficiency of the reduced TPN (TPNH) normally produced by the HMP route is the specific cause of the depressed ability of the diabetic to synthesize fatty acids. A concept of diabetic ketosis is presented based on a block at the site of action of TPNH in fatty acid synthesis.