The effect of acute insulin deprivation on hepatic glucokinase was studied in the intact rat. Liver glucokinase decreased by 30 per cent within 3 hrs. after the intravenous administration of anti-insulin serum (AIS) to fed rats. Hexokinase activity did not change significantly whereas glucose-6-phosphatase activity rose. The administration of glucagon or puromycin failed to decrease glucokinase activity within 3 hrs. despite the fact that the latter agent depressed leucine incorporation into liver protein by 80 per cent. Subcutaneous administration of nicotinic acid significantly reduced the AIS induced fall in glucokinase. In addition, it completely prevented the rise in serum free fatty acids and also diminished the rise in blood glucose. These findings suggest that in acute insulin deprivation the immediate fall in glucokinase activity results from an accelerated rate of enzyme inactivation rather than an inhibition of enzyme synthesis.

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