The Influence of Thyroid State on Hepatic Glycolysis

Abstract

The effects of thyroid status on glycolysis using 10, 20, and 40 mM glucose have been examined in hepatocytes derived from hypothyroid, euthyroid, and hyperthyroid rats. For any given concentration of added glucose, total glycolytic rates, as measured by the release of tritium from [6-3H]glucose, were similar in all thyroid states. The aerobic component of glycolysis, where cytoplasmically generated reducing equivalents are transferred to the mitochondria for oxidation, was the major component in the hyperthyroid state, at all concentrations of glucose. In contrast, the aerobic proportion of glycolysis in the hypothyroid and euthyroid states decreased with increasing concentration of added glucose and the anaerobic component became dominant above 20 mM glucose. Cytoplasmic reducing equivalents generated during aerobic glycolysis were transferred to the mitochondria via both the glycerol 1-phosphate and malate/aspartate shuttles in each thyroid state, even though the former shuttle was considerably depressed in the livers of hypothyroid rats. Both asparagine and aminooxyacetate had only minor effects on the rate of glycolysis, but aminooxyacetate depressed the contribution of aerobic glycolysis whereas asparagine had relatively little influence. The respiration rate in the presence of 40 mM glucose was twice as high in hepatocytes from hyperthyroid rats as in cells from hypothyroid animals, and 1.4 times as high as in hepatocytes from euthyroid rats. Smaller stimulations were observed with lower concentrations of added glucose. Furthermore, the increase in respiratory rate over the endogenous value, induced by 10 mM glucose, was six times higher in cells from hyperthyroid rats than in hepatocytes from hypothyroid animals and 2.7 times higher than that observed with cells from euthyroid rats.The insensitivity of glycolysis to thyroid status in contrast to the marked response of respiration provides additional support for the view that the stimulation of metabolism by thyroid hormone is mediated primarily by its action on mitochondria1 processes.Keywords. Rat hepatocyte; hyperthyroid; hypothyroid; glycolysis.There have been many studies of hepatic glycolysis in normal rats using both perfused liver and isolated hepatocytes [l-71, but no reports of the effects of abnormal thyroid status on hepatic glycolysis, although in vivo glucose turnover as a function of thyroid state has been investigated [8, 91. In aerobic glycolysis, cytoplasmic reducing equivalents are generated through the action of glyceraldehyde-3-phosphate dehydrogenase and are transferred to the mitochondria by means of the glycerol 1-phosphate and malate/aspartate shuttles [lo, 111. Hence, in view of the increase in glycerol 1-phosphate shuttle activity in the liver of hyperthyroid rats [12-141, as well as the permissive effect of thyroid hormone on the induction of hepatic glucokinase [ 151 and the increased metabolic rate associated with hyperthyroidism [16], it might be anticipated that thyroid hormone administration would lead to an increase in th...