Glucoregulatory function of thyroid hormones: interaction with insulin depends on the prevailing glucose concentration.
The effect of elevated serum thyroid hormone concentrations on insulin-induced glucose metabolism was studied in healthy subjects before and after T4 administration (250 micrograms T4/day for 10-14 days). This treatment induced moderate hyperthyroidism (T4, 15.2 micrograms/dl; T3, 200 ng/dl). The following results were obtained. Insulin receptor binding to a 90% enriched monocyte fraction or to mitogen-stimulated cultured T lymphocytes was decreased by T4 administration, whereas insulin binding to erythrocytes was unaffected. Despite down-regulation of cellular insulin receptors, T4 administration did not alter oral glucose tolerance, but increased the disappearance of glucose after an iv load and the amount of glucose metabolized during euglycemic clamp studies infusing 1.0 or 1.5 mU insulin/kg BW X min; no effect was found at insulin infusion rates of 0.5, 2.0, and 4.0 mU/kg X min. At increasing steady state plasma glucose levels (up to 175 mg/dl) and an insulin infusion rate of 1.0 mU/kg BW X min, T4 administration reduced insulin-induced glucose metabolism. We conclude that experimental hyperthyroidism decreases insulin receptor binding but increases insulin-induced glucose metabolism during euglycemia. This may be due to the direct effect of thyroid hormones on glucose metabolism; however, during hyperglycemia, thyroid hormone induced insulin resistance is unequivocal.
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D006980:Hyperthyroidism / Q000097:blood / Q000139:chemically induced; D007263:Infusions, Parenteral; D007328:Insulin / Q000502:physiology*; D008297:Male; D011972:Receptor, Insulin / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D013963:Thyroid Hormones; D011972:Receptor, Insulin; D013974:Thyroxine