Enhanced gluconeogenic capacity from glycerol in hyperthyroid man: evidence in favour of a beta-adrenergic mechanism.

We have previously shown that gluconeogenesis, assessed by glycerol clearance, is increased in hyperthyroid man. The mechanism underlying this change is uncertain but many of the metabolic changes found in hyperthyroidism are thought to be due to increased catecholamine sensitivity of peripheral tissues. To test the hypothesis that enhanced gluconeogenic capacity from glycerol in hyperthyroidism might be mediated via a beta-adrenergic mechanism we have estimated glycerol clearance in thyrotoxic subjects before and during treatment with a non-selective beta-adrenergic blocking drug propranolol (Inderal LA). Control subjects of similar age and weight were also tested. In hyperthyroid subjects, blood glucose and blood glycerol concentrations were increased but blood lactate, pyruvate and alanine concentrations were normal. Glycerol clearance was increased and followed a double exponential decay with a shortened second component half-time. Endogenous glycerol production was increased three fold. Following beta-blockade blood glucose and blood glycerol concentrations fell although blood glucose concentrations remained above normal values. Glycerol clearance and endogenous glycerol production were also decreased but remained significantly higher than in control subjects. Serum thyroxine and serum triiodothyronine concentrations showed no significant change although mean values fell by 10% and 17% respectively. We conclude that the increase in gluconeogenic capacity from glycerol in hyperthyroid subjects is mediated in part by a beta-adrenergic mechanism.