Comparison of Peripheral Thyroid Hormone Metabolism in Normal Rats and in Rats Receiving Prolonged Glucagon Infusion*

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Abstract
An elevated plasma glucagon concentration and reduced T3 production from T4 have both been observed in several clinical disorders, including hepatic cirrhosis, uremia, diabetes mellitus, and starvation. The question of whether glucagon has a direct effect on T3 production was studied in normal rats infused iv with [125I]T4 or [125I]T3 and 3 μg T4/day, using implanted minipumps. The blood [125I]T4 and [125I]T3 levels maintained a plateau between the fifth and ninth days of infusion. Each animal also received a second minipump, implanted ip, that infused either a diluant solution or 30 μg glucagon/100 g BW· day. After 7 days of continuous infusion, the glucagontreated animals showed a 20% increase in plasma glucose and a 4-fold increase in plasma glucagon from baseline. However, the levels of insulin, T4) and T3 remained unchanged. The MCRs and the disposal rates of T4 and T3) calculated by the constant infusion method, showed T4 and T3 MCRs to be 0.99 ± 0.18 and 11.25 ± 2.52 ml/h-100 g, respectively, and T4 and T3 disposal rates to be 68 ± 10 and 9± 2 ng/h · 100 g; there was no difference between the control animals and the glucagon-infused animals. T3 product on was also determined in vitro from T4 added to a liver homogenate. Compared to control animals, the liver homogenate prepared from glucagon-infused animals showed a modestly higher T3 production rate throughout the 60-min incubation period (P = 0.025-0.05). However, the concentration of nonprotein-bound sulfhydryls was similar in the liver, kidney, brain, muscle, and heart of the two animal groups. In conclusion, glucagon does not have an important regulating role on the peripheral metabolism of thyroid hormone and T3 production in rats.