Streptozotocin causes hyperglycemia and hypoinsulinemia in rats. Striking elevations in hepatic phosphoenolpyruvate carboxykinase, pyruvate carboxylase, hexosediphosphatase and glucose-6-phosphate, and dramatic decreases in glucokinase, pyruvate kinase and 6-phosphogluconate dehydrogenase are observed in these diabetic animals. Daily treatment of insulin in diabetic rats brings about increase in liver weight, glycogen and soluble protein contents, and in the levels of glucokinase, pyruvate kinase, 6-phosphogluconate dehydrogenase and lactate dehydrogenase. In terms of unit/gm. liver, the activities of PEP carboxykinase, glucose-6-phosphatase and hexosediphosphatase are depressed by insulin injection. However, a multiphasic pattern is observed in the changes of these gluconeogenic enzymes following insulin treatments when their activities are expressed as units/100 gm. body weight or unit/mg. protein. Insulin withdrawal causes immediate rise in gluconeogenic enzymes, particularly in the extramitochondrial activity of pyruvate carboxylase, and decreases in glucose-catabolizing enzymes which proceed at different rates.

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