Portal vein blood insulin and glucagon are increased in experimental hyperthyroidism.

Decreased glucose tolerance in hyperthyroidism has been long recognized; however, the mechanism(s) responsible for altered carbohydrate metabolism have not been elucidated. Studies of insulin secretion in hyperthyroidism have been reported by several investigators; however, the results are not conclusive since hormone secretion has been reported as increased, normal, or decreased. Few investigations of glucagon secretion in hyperthyroidism have been described; thus, the role of the alpha cell hormone in the glucose intolerance associated with thyrotoxicosis has not been established. To clarify these matters, experimental hyperthyroidism was induced in male rats by injecting T4 ip for 9 days. On the 10th day, blood was collected from the portal vein for measurement of insulin and glucagon. Animals injected with T4 (500 microgram/kg . day) became clearly thyrotoxic as evidenced by elevated plasma T4 and T3 and diminished weight gain. Rats receiving 750 micrograms T4/kg demonstrated marked enhancement of pancreatic insulin and glucagon release as evidence by elevated portal vein hormone values. Plasma insulin and glucagon in T4-treated rats were substantially elevated regardless of whether the animals were fed or were fasted for 20 h before blood samples were obtained. Insulin and glucagon in vena cava blood were far lower than in the portal vein in both control and hyperthyroid rats, and there was no significant difference between the two groups. We believe that portal vein hormone concentrations more accurately reflect insulin and glucagon secretion than do peripheral blood levels because the hormones and partially degraded in the liver. It is postulated that elevated T4 stimulates the alpha cell to release excess amounts of glucagon, which enhances hepatic glucose output. The possible increase in hepatic glucose output plus insulin resistance, which is characteristic of hyperthyroidism, may account for a secondary rise in insulin release.