Effect of fructose on lipogenesis from lactate and acetate in diabetic liver.

Defective glucose utilization in the liver of the glucose-fed diabetic rat has been stated to be the result of at least two blocks: one, at an early stage in glycolysis, probably hexokinase; the other, in the synthesis of fatty acids from the Z-carbon-like intermediate. This conclusion was based on the following observations: (1) the conversion of C14-glucose to CO2 was depressed in the liver of the alloxan-diabetic rat, whereas the rate of CY402 formation from C14-fructose proceeds at normal rates (1) ; (2) the incorporation of C14-labeled glucose, fructose, lactate, and acetate into fatty acids by diabetic hepatic tissue was markedly depressed (l-3) ; and (3) the liver of the alloxan-diabetic rat treated with large doses of insulin for 2 to 3 days showed an extraordinary increase in its capacity to synthesize fatty acids from glucose, lactate, and acetate (3, 4). The above experiments were carried out with livers of rats that had been fed a 58 per cent glucose diet. The finding that fructose is more readily oxidized to CO2 than is glucose by the diabetic liver led us to study the effect of previous fructose feeding on hepatic lipogenesis. The incorporation of lactate-2-Cl4 and acetate-l ,2-Cl4 into fatty acids was compared in livers of two groups of diabetic rats. One group was fed a diet containing 58 per cent fructose for 4 days before being sacrificed, the other a diet containing 58 per cent glucose for the same number of days. The fructose feeding resulted in a pronounced increase in the capacity of the diabetic rat liver to convert lactate and acetate to fatty acids, an increase, it should be noted, that occurred without the administration of insulin. This fructose feeding did not repair the defective utilization of CY4-glucose in the diabetic liver. Our findings thus suggest that impaired lipogenesis from the 2-carbon-like intermediate in the liver of the glucose-fed alloxandiabetic rat need not be the result of insulin lack per se, but may be secondary to the initial or primary block in glucose utilization.