The effect of thyroid hormones on gluconeogenesis and forearm metabolism in man

The present study was designed to examine the effects of excess T3 on total body glucose production and forearm exchange of glucose, amino acids, and other metabolites. Five healthy male volunteers were studied after an overnight fast, before and 7 days after the administration of 150 micrograms/day T3. Glucose production (milligrams per kg/min) was measured using a primed continuous infusion of [3-3H]glucose and gluconeogenic index (micromoles per kg/min) was measured by following the conversion of infused [14C]alanine to [14C]glucose. Blood flow across the forearm was measured using capacitance plethysmography and forearm release of substrates was determined by the Fick principle. After T3 administration, there was a 3.7-fold rise in T3 from 150 +/- 15 to 530 +/- 12 ng/dl (P less than 0.001), with no change in insulin (12 +/- 1 microU/ml pre-T3 vs. 13 +/- 2 microU/ml post-T3) and glucagon (79 +/- 5 pre-T3 vs. 84 +/- 7 pg/ml post-T3). T3 administration resulted in an increase in plasma glucose (from 83 +/- 5 to 98 +/- 5 mg/dl; P less than 0.05), net glucose uptake by the forearm (from 250 +/- 90 to 712 +/- 60 nmol/100 ml forearm tissue X min; P less than 0.005) and glucose production (1.7 +/- 0.09 to 2.2 +/- 0.08 mg/kg X min; P less than 0.005), without a change in glucose clearance (2.1 +/- 0.02 vs. 2.0 +/- 0.02 ml/kg X min); the rate of conversion of [14C]alanine to [14C]glucose increased by 30% (0.56 +/- 0.03 to 0.74 +/- 0.03 mumol/ kg X min P less than 0.005). These values were associated with a 25% increase in blood lactate to 712 +/- 69 mumol/liter (P less than 0.05) and a 131% increase in lactate release across the forearm to 434 +/- 90 (P less than 0.005). Forearm release of alanine (96 +/- 29 nmol/100 ml forearm tissue X min) and glutamine (151 +/- 41 nmol/100 ml forearm tissue X min) increased by 90% (P less than 0.005 and P = 0.04, respectively), with no change in their concentrations. Forearm release of branched chain amino acids did not change, while those of their ketoacids, alpha-ketoisocaproate (KIC) and alpha-ketoisovalerate (KIV), doubled (to 64 +/- 9 mumol/liter for KIC and 39 +/- 6 mumol/liter for KIV; P less than 0.05). These were associated with a 45% increase in the branched chain amino acid levels and a 46% rise in both KIC and KIV levels to 41 +/- 9 and 28 +/- 7 mumol/liter, respectively (P less than 0.05). There was a concurrent significant (P less than 0.05) change in the arterial levels of phenylalanine (-32%), tyrosine (-29%), threonine (-20%), glycine (-20%), and serine (-15%), without any change in their efflux across the forearm. The data indicate that a pharmacologically induced rise in T3, to levels comparable to those seen in hyperthyroidism, results in enhanced glucose production, with an increase in glucose uptake by the forearm. The former can be partially accounted for by an increase in hepatic gluconeogenesis, glycogenolysis, or possibly increased renal glucose production...