Fluctuation of hepatic enzymes important in glucose metabolism in relation to thyroid function.

Abstract

Enzyme activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, pyruvate kinase and of mitochondrial glycerolphosphate dehydrogenase were studied in the livers of rats under the following states of thyroid function: 131I‐thyroidectomized rats, 131I‐thyroidectomized rats treated with triiodothyronine, normal rats treated with excess of triiodothyronine, and normal untreated rats. In the thyroidectomized group all of the enzyme activities listed were significantly diminished. After treatment with a single dose of triiodothyronine the activities of pyruvate carboxylase and of pyruvate kinase were restored to normal whereas phosphoenolpyruvate carboxykinase and — most markedly — glycerolphosphate dehydrogenase were raised above the normal level. After repeated administration of triiodothyronine to normal rats a further increase in the activity of pyruvate carboxylase, phosphoenolpyruvate carboxykinase and of glycerolphosphate dehydrogenase was observed.The activities of glycerolphosphate dehydrogenase and of pyruvate carboxylase 70 h following triiodothyronine injection into hypothyroid rats were more than 50% lower after treatment with actinomycin C suggesting that the increase in enzyme activities was due to increased synthesis of enzyme protein. Phosphoenolpyruvate carboxykinase activity was not changed significantly by actinomycin C.The possible significance of these thyroid hormone dependent enzyme fluctuations in controlling the overall rate of hepatic gluconeogenesis is discussed.