Fatty Acid Oxidation, Oxidative Phosphorylation and Ultrastructure of Mitochondria in the Diabetic Rat Liver: Hepatic Factors in Diabetic Ketosis

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Abstract
Oxidative phosphorylation, maximum rate of palmitate xidation and ultrastructure of mitochondria (MT) were tudied in livers of ketotic, nonketotic and insulin-treated liabetic rats. Significant changes in oxidative phosphorylaion were found only in ketotic diabetes. Respiratory control atios were decreased for all of the substrates studied and vere primarily due to increased state 4 respiration with lalmitylcarnitine and 2-oxoglutarate, and lowered state 3 espiration in the case of succinate. ADP/O ratio was only partially lowered with 2-step oxidation of 2-oxoglutarate. The naximum rate of palmitate oxidation to acetoacetate was ncreased 90 per cent in MT of rats with ketotic diabetes ind 50 per cent in MT from animals with nonketotic diabetes. Accompanying these changes were ultrastructural alteritions of MT. The average size of MT in the diabetic rat liver was 50 per cent larger in cut sections. MT within hepacocytes in ketotic diabetes were distorted, enlarged, and had irregular shapes and contours. Cristae tended to be deranged; when isolated, crescentic MT were predominant, In the insulin-treated diabetic rats, these functional and morphological changes were not observed. The results imply that in diabetic ketosis, increased availability of free fatty acid(s) (FFA) in hepatocytes together with increased capacity of mitochondrial FA oxidation produces more acetyl CoA which in turn results in an overproduction of ketone bodies. Since a significant increase in state 4 respiration of MT isolation from ketotic diabetic rats was observed, FA oxidation may proceed independently of ADP availability because of “loose” coupling of respiration to phosphorylation.

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