Glucose Metabolism in Experimental Hyperthyroidism: Intactin VivoSensitivity to Insulin with Abnormal Binding and Increased Glucose Turnover

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Abstract
The characteristics of the dose response of insulin on the glucose turnover rate and erythrocyte insulin binding parameters were determined in five normal men before and during experimentally induced hyperthyroidism [L-T4) (2 εg kg−1 day−1) for 4 weeks with additional L-T3 (1 εg kg−1 day−1 for the following 3 weeks]. Hyperthyroidism was characterized by significant rises in T3 from 1.92 ± 0.17 (±SEM) to 3.66±0.17 nmol/liter (P < 0.01) and resting metabolic rate from 39 ± 0.7 to 48 ± 1 watt/m2 (P < 0.001). While the subjects received a diet adapted to the metabolic rate, blood glucose rose from 3.8 ± 0.07 t o 4.46 ± 0.11 mmol/liter (P < 0.05) without a significant change in plasma insulin. During the insulin dose-response study, glucose infusion rates were unaltered by hyperthyroidism, and neither the maximum effect nor the sensitivity to insulin was altered. Glucose turnover rate, measured using [6,6-2H2]glucose as)tracer, was determined in the basal state and during the 0.4 mU kg−1 min−1 insulin infusion. In the basal state, it was significantly increased by hyperthyroidism (control, 2.3 ± 0.1; hyperthyroid-ism, 3.7 ± 0.1 mg kg−1 min−1. During the insulin infusion, hepatic glucose production was totally suppressed before T4 and T3 treatment, but was 0.96 ± 0.39 mg kg−1 min−1 during T4 and T3 treatment. A marked decrease in the insulin binding affinity o t erythrocytes was found without a change in the insulin receptor number. In conclusion, glucose metabolism in experimental hyperthy-roidism is characterized by 1) increases in basal glucose production and utilization; 2) antagonism between the effect of insulin and hyperthyroidism at the hepatic level; and 3) lack of peripheral insulin resistance in spite of marked alteration in erythrocyte insulin binding affinity.