Thyrotropin-releasing hormone potently reverses epinephrine-stimulated hyperglycemia in mice.
Intracerebroventricular microinjection of thyrotropin-releasing hormone (TRH) potently blocked the development of, as well as promptly reversed, epinephrine-stimulated hyperglycemia in mice. The central antihyperglycemic effect was dose-related (0.1-10 micrograms), could be reproduced by an intravenous injection of a large dose of the peptide (100 micrograms), was independent of experimental factors such as stress and age, was effective against other hyperglycemic stimuli, and appeared to be unique to TRH, as it could not be mimicked by many other centrally active peptides known to influence glucoregulation in normoglycemic animals. Moreover, the antihyperglycemic effect of TRH appeared to depend on the structural integrity of the peptide molecule but seemed to be unrelated to the peptide's hypophysiotropic actions or to interaction of the peptide with previously characterized TRH receptors, as it could be mimicked by various analogs devoid of thyrotropin- and prolactin-releasing influences or by peptides resembling TRH in amino acid composition but lacking substantial binding affinity to TRH receptors. Furthermore, the effect of TRH to reverse epinephrine-stimulated hyperglycemia appeared to be mediated by combined action of peripheral sympathetic and parasympathetic mechanisms to stimulate insulin release from the pancreas, since only complete blockade of the central autonomic outflow, but not selective perturbation of the sympathetic or parasympathetic outflow, or depletion of pancreatic insulin could substantially attenuate the antihyperglycemic action. Taken together, these results suggest a new physiologic role of TRH as a central glucoregulatory neuropeptide involved in autonomic modulation of insulin secretion and prevention of hyperglycemia.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006943:Hyperglycemia / Q000139:chemically induced; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009479:Neuropeptides / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*
D001786:Blood Glucose; D009479:Neuropeptides; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D004837:Epinephrine