Triiodothyronine increases splanchnic release and peripheral uptake of glucose in healthy humans.

To examine the effect of experimental hyperthyroidism induced by triiodothyronine (T3) administration on glucose utilization and glucose-stimulated insulin secretion, euglycemic insulin clamp studies (A), hyperglycemic clamp studies (B), and estimation of splanchnic glucose metabolism after an oral glucose load by means of the hepatic venous catheter technique (C) were performed in healthy volunteers whose serum T3 concentration had been increased from 1.1 +/- 0.02 (SE) to 3.5 +/- 0.2 ng/ml. At plasma insulin concentrations of 77 +/- 6 microU/ml and maintenance of euglycemia, insulin-mediated glucose metabolism (6.8 +/- 0.4 mg X kg-1 X min-1) was not significantly altered following T3 exposure (7.2 +/- 0.7) in study A. When plasma glucose was raised and maintained at 7 mmol/l above basal, glucose uptake (10.6 +/- 0.7 mg X kg-1 X min-1) was increased to 14.6 +/- 2.0 mg X kg-1 X min-1 (P less than 0.02) following T3 administration in study B. In study C, basal splanchnic glucose output (104 +/- 10 mg/min) was markedly augmented when preceded by T3 exposure (167 +/- 17 mg/min; P less than 0.005). After a 75-g glucose load, splanchnic glucose output was enhanced by T3 by 30% (43.4 +/- 2.2 vs. 56.9 +/- 6.6 g/150 min; P less than 0.05), whereas arterial plasma concentrations of glucose, insulin, and C-peptide were not significantly different. It is concluded that in healthy humans, exposure to elevated plasma concentrations of T3 increases the amount of glucose to be released from the splanchnic bed. Glucose tolerance, however, remains unaltered, because peripheral glucose uptake is increased at the same time.