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

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 micrograms kg-1 day-1) for 4 weeks with additional L-T3 (1 microgram 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 less than 0.01) and resting metabolic rate from 39 +/- 0.7 to 48 +/- 1 watt/m2 (P less than 0.001). While the subjects received a diet adapted to the metabolic rate, blood glucose rose from 3.8 +/- 0.07 to 4.46 +/- 0.11 mmol/liter (P less than 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; hyperthyroidism, 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 to erythrocytes was found without a change in the insulin receptor number. In conclusion, glucose metabolism in experimental hyperthyroidism 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.

Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways

“…However, there was no evidence of peripheral insulin resistance, possibly because of the compensatory increase in muscle GLUT4 expression leading to muscle with normal levels of GLUT4 protein. This pattern of increased EGP and hepatic insulin resistance is similar to the pattern seen in previous reports of human and canine hyperthyroid models (12,25,41,56) and mirrors the pattern seen with chow-fed T 4 -induced thyrotoxic rats (22). In contrast, KB-2115 did not increase glycerol turnover and did not result in hepatic insulin resistance.…”

Acute regulation by insulin of phosphatidylinositol-3-kinase, Rad, Glut 4, and lipoprotein lipase mRNA levels in human muscle.

“…Insulin (Actrapid; Novo, Copenhagen, Denmark) was infused at 12 pmol/kg per min for 3 h. The insulin infusion rate was primed according to Rizza et al (16). Any decrease in blood glucose was prevented by the infusion of 20% glucose (Aguettant, Lyon, France) as described previously (17). After 3 h of euglycemic clamp, a second muscle biopsy was obtained from the opposite thigh.…”

The expression of ob gene is not acutely regulated by insulin and fasting in human abdominal subcutaneous adipose tissue.

“…Seven subjects suffered from morbid obesity (body mass index (BMI) 1 ), from whom six underwent a 3-h euglycemic hyperinsulinemic clamp (insulin infusion rate of 12 pmol/Kg.min) (25) in order to determine the acute effect of insulin on ob gene expression. The study was performed after an overnight fast.…”