Studies of the Metabolic Effects of Acute Insulin Deficiency: II. Changes in Hepatic Glycolytic and Krebs-Cycle Intermediates and Pyridine Nucleotides

Abstract

(1) Various glycolytic and Krebs-cycle intermediates and pyridine nucleotides were measured in the livers of anti-insulin serum treated (i.e., acute insulin deprivation) and alloxan diabetic rats (i.e., chronic insulin deprivation). (2) Acute insulin deprivation of three-hour duration resulted in significant changes in the concentration profile of the various glycolytic intermediates suggesting marked impairment of glycolysis at the phosphofructokinase step, activation of glycogenolysis, and decreased hexosemonophosphate shunt activity. The tissue levels of citrate and malate were not elevated under these conditions. (3) Insulin deficiency of forty-eight hours' duration produced changes in the hepatic levels of glycolytic and Krebs-cycle intermediates which differed in several important aspects with those seen in acute insulin deficiency. The accumulation of P-pyruvate and 3-P-glycerate in forty-eight hour alloxan diabetic rats, when gluconeogenesis is accelerated, suggests that the rate limiting step in this system resides at some step between the conversion of 3-P-glycerate and dihydroxyacetone-P. (4) Acute insulin deficiency of three-hour duration produced no significant changes in the levels of oxidized and reduced pyridine nucleotides. Chronic insulin deficiency (48hr. alloxan diabetic rats) did not alter the content of TPN, TPNH or DPN but did cause a significant decrease (32 per cent) in the level of DPNH.