243 THE INSULIN/GLUCAGON RATIO AFFECTS MITOCHONDRIAL ADENINE NUCLEOTIDE ACCUMULATION AND PYRUVATE CARBOXYLATION IN NEWBORN RABBIT LIVER

Abstract

We have shown that a rapid postnatal increase in hepatic mitochondrial adenine nucleotide content and the matrix ATP/ADP ratio activates pyruvate carboxylation (a matrix reaction) thereby stimulating gluconeogenesis in the newborn rabbit (Ped.Res. 1983, 17:129). Here we examined the role of insulin and glucagon as initiating stimuli for this phenomenon. Manipulation of the insulin/glucagon ratio in vivo by insulin injection at birth delayed postnatal increases in mitochondrial adenine nucleotide content and pyruvate carboxylation (65 and 69% of controls respectively at 2 hrs after birth). Conversely, glucagon injection produced a supranormal increase in both mitochondrial adenine nucleotide content and pyruvate carboxylation (114 and 1195% of control respectively at 2 hrs postnatal). In addition, insulin injection prevented, while glucagon enhanced the normal postnatal increase in the cellular ATP/ADP ratio (2 fold decrease and 1.3 fold increase respectively by 1 hr after birth). These results show that a decreased insulin/glucagon ratio promotes the rapid movement of adenine nucleotides from the liver cytosol into the mitochondrial matrix. The increased matrix concentration of ATP stimulates pyruvate carboxylation, thereby activating gluconeogenesis during very early postnatal life. The results also suggest that persistent hypoglycemia in infants born to diabetic mothers may be due to a delay in the onset of postnatal gluconeogenesis that is secondary to a higher than normal insulin/glucagon ratio. (NIH HD 16936)

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