Effects of thyroid states on the Cori cycle, glucose-alanine cycle, and futile cycling of glucose metabolism in rats

Abstract

The effect of thyroid status on glucose recycling was measured in intact rats by comparing the fates of differently labeled [ 3H]- and [ 14C]glucose. Glucose recycling at the level of three-carbon compounds (i.e., Cori and glucose-alanine cycles) was measured by comparing the rates of turnover of [6- 3H]- and [6- 14C]glucose in the same animal. The rate of recycling increased (33–110%) in hyperthyroid rats and decreased (22–30%) in hypothyroid (thyroidectomized) rats. The relative importance of the Cori and glucose-alanine cycles was measured by analyzing the labeled glycolytic intermediates after the injection of labeled glucose; and by measuring the rate of glucose production from the infused labeled lactate and alanine. The results showed that the rate of the Cori cycle is much greater than the glucose-alanine cycle in rats. Substrate cycling at the level of glucokinase-glucose-6-phosphatase was measured by comparing the rates of turnover of [2- 3H]- and [6- 3H]glucose; and phosphofructokinase-fructose bisphosphatase was measured by comparing the rates of turnover of [3- 3H]- and [6- 3H]glucose. These cycles were also affected by thyroid states of the animals. The rate of the phosphofructokinase-fructose bisphosphatase cycle increased threefold in hyperthyroid rats and decreased by about half in hypothyroid rats. The glucokinase-glucose-6-phosphatase substrate cycle occurred at the rate of nearly 2 μmol/min/100 g body wt in the hyperthyroid, fasted rats; it was not detectable in hypo- or euthyroid rats. The contribution of the energy released by these cycles to thyroid thermogenesis was discussed. Effects of thyroid states on glucose metabolism in perfused muscles were also studied. There is an apparent shift in the source of energy for oxidation in the hyperthyroid rat. The ratio of lactate production to glucose uptake was significantly elevated in the hyperthyroid rats. This change predisposes for increased glucose recycling in hyperthyroid rats to avoid lactate accumulation and acidosis.