Thyrotropin-releasing hormone increases plasma levels of glucagon, insulin, glucose and free fatty acids in rabbits.

Abstract

The hypothalamus is known to participate in the control of carbohydrate and lipid metabolism and, therefore, the hypothalamic thyrotropin-releasing hormone, TRH, could possibly be involved in these control functions. Moreover, TRH immunological and biological activities have been demonstrated in the pancreatic islets, but experiments with isolated rat pancreas have failed to show any direct stimulatory effect of TRH on glucagon and insulin release. In order to study any in vivo effects of TRH on the pancreatic hormone release and the plasma levels of glucose and free fatty acids, TRH was injected intravenously into fasted rabbits, and blood samples obtained from the marginal ear vein. Dose-related increases in plasma levels were observed for glucagon, insulin, glucose and free fatty acids down to a dose of 0.4 microgram TRH. Corresponding experiments showed that the tripeptide pyroGlu-His-GlyOH was inactive. The increase of plasma levels of glucagon was augmented by simultaneous injection of TRH and insulin, and was suppressed in rabbits which were fed or infused with somatostatin. This suggests that TRH may have physiological significance in modulating the plasma levels of glucagon, insulin, glucose and free fatty acids. In contrast to the effect of alanine, the increase in plasma levels of glucagon by TRH was not significant during the first 10 minutes. This suggests that the effect to TRH on glucagon and insulin release is indirect.