Thyrotropin-releasing hormone blocks neurally-mediated hyperglycemia through central action.

Central injection of thyrotropin-releasing hormone (TRH) potently blocked the development of, as well as rapidly reversed, 2-deoxyglucose (2-DG)-stimulated hyperglycemia in mice. The antihyperglycemic effect was dose-related, dependent upon the structural integrity of the peptide, dissociated from the peptide's hypophysiotropic action and from its interaction with TRH receptors, and mediated by the cholinergic parasympathetic system. Moreover, TRH blocked the rise in plasma glucose following central injection of corticotropin-releasing factor, enkephalin, clonidine and glucagon, as well as the hyperglycemic response to immobilization, electric foot shock or endotoxin administration. These results indicate that TRH, acting within the central nervous system, can block neurally-mediated hyperglycemia in addition to its previously reported actions to elicit systemic hypoglycemia in normoglycemic mice and to antagonize epinephrine-stimulated hyperglycemia in these animals.