EFFECTS OF THYROID STATUS ON GLUCOSE CYCLING BY ISOLATED RAT HEPATOCYTES

The effects of alterations in thyroid status on glucose metabolism hav e been investigated in rat hepatocytes. Addition of 10 or 40 mmol/L gl ucose induced increases in respiration rate that were significantly la rger in cells from hyperthyroid rats than from hypothyroid animals. Th e responses of hepatocytes from euthyroid rats were intermediate. In c ells from hyperthyroid rats, most of the increase occurred upon additi on of 10 mmol/L glucose, with only a further small stimulation resulti ng when glucose concentration was increased to 40 mmol/L. For a given glucose concentration, glycolytic rates, determined by measuring relea se of tritium from [6-H-3]glucose, were comparable in all thyroid stat es. Studies with 10 mmol/L [2-H-3]glucose showed that cycling between glucose-6-phosphate and glucose was almost twofold higher in euthyroid and hyperthyroid states as compared with the hypothyroid state, altho ugh the magnitude of the increase in cycling rate was only approximate ly 0.2 mu mol glucose . min(-1). g(-1). When 40 mmol/L [2-H-3]glucose was added, over 44% of the glucose that was phosphorylated to glucose- 6-phosphate was cycled back to glucose, but this cycling was independe nt of thyroid status. Cycling between fructose-1,6-bisphosphate and fr uctose-6-phosphate was negligible in all thyroid states. Rates of glyc ogen synthesis were comparable in hypothyroid and hyperthyroid states and slightly less than in the euthyroid state. Glycolytically formed p yruvate was cycled back to glucose in hepatocytes from hypothyroid, eu thyroid, and hyperthyroid rats. During a 60-minute incubation period, cycling to glucose in the presence of 10 mmol/L or 40 mmol/L glucose w as up to twofold higher in cells from euthyroid and hyperthyroid rats than in hepatocytes from hypothyroid animals. The measured increases i n cycling rates induced by thyroid hormone were small and in theory co uld have been satisfied by a much smaller increase in respiration rate than was observed. Copyright (C) 1996 by W.B. Saunders Company