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.

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By using a modified Scatchard analysis, statistically significant differences were observed between the receptor affinities of the groups A aiid D, B and D, A and C.The receptor affinities and concentrations were not significantly different between the follicular and the luteal phases. From the data, no inverse correlation between the plasma insulin concentration and receptor binding was seen, i.e. the phenömenon of downiegulation pf insulin receptor concentration with hyperinsulinaemia seemed not to apply to erythrocytes.The present results suggest that insulin binding to erythrocytes is mpdulated preferably or even exclusively by an alteration of receptor affinity and that short-term chariges in insulin binding to erythroeytes are not caused by an alterätion of receptor concentration. Vergleich der Bindung von Insulin an Erythrocyten während und nach Schwangerschaft und in der Proliferationsund der Sekretionsphase des Menstruations-Cyclus

Capillary radioimmunoassay -- a modification of the coated tube technique -- is described. The assay is equivalent (accuracy, sensitivity, precision) to conventional methods for insulin determination; it overcomes, however, the necessity of centrifugation or filtration and offers the added bonus of being automation compatible.