Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans

Abstract

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)

IGF-I increases the recruitment of GLUT4 and GLUT3 glucose transporters on cell surface in hyperthyroidism

“…In agreement with previous results, glucose tolerance was impaired in the hyperthyroid subjects (2, 16); this is due to the insulin resistance primarily at the liver since glucose uptake in peripheral tissues is generally found to be either normal or increased (2,16,17).…”

“…In hyperthyroidism, absolute rates of glucose transport in peripheral tissues (such as muscle or adipose tissue) are found to be increased, in order to adapt to high energy demand (2,16,17). Our results suggest that hyperthyroidism increases the sensitivity of the recruitment of GLUT3 and GLUT4 transporters to the cell surface in response to IGF-I, thus contributing to increased glucose transport rates.…”

“…In a previous study, lipid metabolism was investigated in mouse monocytes after incubation with [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]oleate (33). Of the radioactivity associated with lipid, 80% of oleate was shown to be incorporated into triglycerides, 18% was incorporated into phospholipids, and 2% was recovered as non-esterified fatty acids.…”

“…To adapt to high energy demand, cellular rates of basal and insulin-stimulated glucose disposal are generally elevated to increase the rates of glucose oxidation and lactate formation; lactate is then used by the liver to increase the rates of gluconeogenesis and endogenous glucose production (1,2).…”

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

“…In clinical hyperthyroidism (HR), impaired glucose tolerance and inulin resistance are frequent findings (1)(2)(3)(4)(5). In HR, tissue metabolic rate increases significantly (1).…”