The Effect of Thyroid Hormones on Gluconeogenesis and Forearm Metabolism in Man

Abstract

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 µg/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 < 0.001), with no change in insulin (12 ± 1 µ/ml pre-T₃vs. 13 µ 2 /U/ml post-T₃) and glucagon (79 ± 5 pre-T₃vs. 84 ± 7 pg/ml post-T₃). T₃ administration resulted in an increase in plasma glucose (from 83 ± 5 to 98 ± 5 mg/dl; P < 0.05), net glucose uptake by the forearm (from 250 ± 90 to 712 ± 60 ±mol/100 ml forearm tissue-min; P < 0.005) and glucose production (1.7 ± 0.09 to 2.2 ± 0.08 mg/kg-min; P < 0.005), without a change in glucose clearance (2.1 ± 0.02 vs. 2.0 ± 0.02 ml/kg-min); the rate of conversion of [¹⁴C]alanine to [¹⁴CJglucose increased by 30÷ (0.56 ± 0.03 to 0.74 ± 0.03 <mol/ kg-min P < 0.005). These values were associated with a 25÷ increase in blood lactate to 712 ± 69 <mol/liter (P < 0.05) and a 131÷ increase in lactate release across the forearm to 434 ± 90 (P < 0.005).

Forearm release of alanine (96 ± 29 nmol/100 ml forearm tissue-min) and glutamine (151 ± 41 nmol/100 ml forearm tissue-min) increased by 90÷ (P < 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, α-ketoisocaproate (KIC) and α-ketoisovalerate (KIV), doubled (to 64 ± 9 µmol/liter for KIC and 39 ± 6 <mol/ liter for KIV; P < 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 <mol/liter, respectively (P < 0.05). There was a concurrent significant (P < 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 increse 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. The increased peripheral glucose utilization could be directly or indirectly due to an effect of T³ on skeletal muscle. Furthermore, excess T³ resulted in both enhanced proteolysis and lipolysis. These resemble in many ways the in vitro metabolic effects of T³. (J Clin Endocrinol Metab56: 479, 1983)