Mechanisms of sympathoadrenal failure and hypoglycemia in diabetes.
A reduced sympathoadrenal response, induced by recent antecedent hypoglycemia, is the key feature of hypoglycemia-associated autonomic failure (HAAF) and, thus, the pathogenesis of iatrogenic hypoglycemia in diabetes. Understanding of the mechanism(s) of that reduced response awaits new insight into its basic molecular, cellular, organ, and whole-body physiology and pathophysiology in experimental models. In this issue of the JCI, McCrimmon and colleagues report that application of urocortin I (a corticotrophin-releasing factor receptor-2 agonist) to the ventromedial hypothalamus reduces the glucose counterregulatory response to hypoglycemia in rats (see the related article beginning on page 1723). Thus, hypothalamic urocortin I release during antecedent hypoglycemia is, among other possibilities, a potential mechanism of HAAF.
Cryer
Philip E
PE
Division of Endocrinology, Metabolism and Lipid Research, General Clinical Research Center, and Diabetes Research and Training Center, Washington University School of Medicine, St. Louis, Missouri 63110, USA. pcryer@wustl.edu
D000311:Adrenal Glands / Q000502:physiology*; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D048909:Diabetes Complications / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism; D051381:Rats; D054832:Urocortins; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
D007328:Insulin; D054832:Urocortins; D005934:Glucagon; D003346:Corticotropin-Releasing Hormone