AJP - Endocrinology and Metabolism, Vol 248, Issue 5 593-E601, Copyright © 1985 by American Physiological Society
Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans
G. Dimitriadis, B. Baker, H. Marsh, L. Mandarino, R. Rizza, R. Bergman, M. Haymond and J. Gerich
To determine the effect of thyroid hormone excess on insulin secretion,
metabolism and action in humans, we examined intravenous glucose tolerance,
glucose-induced insulin secretion, insulin clearance, monocyte insulin
receptor binding, and the dose-response characteristics for the effects of
insulin on glucose production, uptake, oxidation, and nonoxidative disposal
in 10 normal volunteers for 14 days before and after oral administration of
triiodothyronine (T3) in doses that increased plasma T3 to levels observed
in spontaneous thyrotoxicosis (P less than 0.001). After T3 postabsorptive
plasma glucose (P less than 0.05) and insulin (P less than 0.05) both
increased; intravenous glucose tolerance was unaffected, but plasma insulin
responses were increased (P less than 0.01); basal glucose production,
uptake, and oxidation all increased (all P less than 0.05), whereas
nonoxidative glucose disposal was unaffected (P = NS); monocyte insulin
receptor binding increased (P less than 0.01) due to increased receptor
affinity (P less than 0.05); and receptor number was not significantly
altered (P = NS). Insulin clearance was increased. Insulin-induced
suppression of glucose production was impaired (Km 22 +/- 3 vs. 37 +/- 7
microU/ml, P less than 0.02); maximal insulin-induced glucose uptake (10.7
+/- 0.6 vs. 13.0 +/- 0.9 mg X kg-1 X min-1, P less than 0.001) and
oxidation (3.41 +/- 0.30 vs. 5.34 +/- 0.59 mg X kg-1 X min-1, P less than
0.001) were increased without a significant change in Km. However,
submaximal rates of nonoxidative glucose disposal and glucose uptake were
inappropriately low for the increased insulin receptor binding.(ABSTRACT
TRUNCATED AT 250 WORDS)
