Thyrotropin-releasing hormone (TRH): Insulin-like action on glucoregulation

Abstract

Normoglycemia is maintained through a complex interplay between the glucoregulatory hormones, glucagon, epinephrine. the glucocorticoids and insulin [l, 21, and it is under the controlling influence of various neurotransmitters and peptides acting upon the endocrine pancreas, the liver or at the level of the central nervous system (CNS) [3-6]. Most of the hormones and neural factors implicated in glucoregulation are called into play in response to hypoglycemia resulting from diminished supply or increased expenditure of metabolic fuel, and they act to normalize glucose levels by directly or indirectly promoting sugar production [7]. For example, glucagon is released from alpha-cells in the pancreas whenever plasma glucose levels fall below normal, and it stimulates glucose production in the liver through direct action [ 1,8] or, additionally, by acting within the CNS [9]. Similarly, epinephrine is released from the adrenal medulla in response to hypoglycemia, and it promotes glucose production through direct action on muscle or liver [ 1, 101 as well as indirectly, through CNS action [ll]. Other factors, such as cholecystokinin, bombesin, the opioid peptides and corticotropin-releasing factor (CRF), influence glucoregulation in part by modulating pancreatic function and in part by indirectly stimulating glucose production through CNS action [4, 12-151. In contrast to the multitude of apparently redundant counterregulatory mechanisms set in motion by hypoglycemia, only one peptide hormone, insulin. serves to counteract hyperglycemia. Insulin is released from pancreatic beta-cells in response to high glucose, and it normalizes sugar levels partly by stimulating glucose utilization in muscle and adipose tissues and partly by inhibiting glucose output from the liver [16, 171. In addition, insulin can lower circulating glucose levels by indirectly modulating the production and utilization of sugar through action in the CNS [lS-211. Thyrotropin-releasing hormone (TRH) is a hypothalamic tripeptide (pGlu-His-Pro-NH,) implicated in the regulation of pituitary thyrotropin and prolactin synthesis and secretion [22,23]. In addition. it is known for its many extrapituitary actions. Most