title: Maintaining euglycemia prevents insulin-induced Fos expression in brain autonomic regulatory circuits.
abstract: OBJECTIVE
  Insulin-induced hypoglycemia activates neurons in hypothalamic and brain medullary nuclei involved in central autonomic regulation. We investigated whether these central neuronal activations relates to a deficiency of glucose supply.
  
  
  METHODS
  Three groups of non-fasted, conscious rats received intravenous (iv) saline infusion (control), a hyperinsulinemic/hypoglycemic clamp, or a hyperinsulinemic/euglycemic clamp for 120 minutes and then the brains were collected for Fos immunohistochemistry.
  
  
  RESULTS
  The number of Fos positive cells significantly increased in the paraventricular nucleus of the hypothalamus (PVN, 191 +/- 63 versus 66 +/- 18), pontine locus coeruleus (LC, 53 +/- 19 versus 5 +/- 2), brain medullary dorsal motor nucleus of the vagus (DMV, 26 +/- 4 versus 1 +/- 0), and nucleus tractus solitarii (NTS, 38 +/- 3 versus 10 +/- 35) in rats with hyperinsulinemic/hypoglycemic clamp compared with the controls. Maintaining blood glucose levels within physiological range by hyperinsulinemic/euglycemic clamp prevented insulin infusion-induced Fos expression in the PVN, DMV, and NTS. The numbers of Fos positive cells in these nuclei were significantly lower (-87%, -75%, and -51%, respectively) than that in the hypoglycemic rats.
  
  
  CONCLUSIONS
  These results indicate that neuronal activation in hypothalamic and medullary autonomic regulatory nuclei induced by insulin administration is caused by hypoglycemia rather than a direct action of insulin. In addition, certain neurons in the medullary DMV and NTS respond to declines in glucose levels within physiological range.
authors: Department of Medicine, Division of Digestive Diseases and Brain Research Institute, UCLA, Los Angeles, CA 90073, USA.
authors: Yan
authors: Y
authors: Ao
authors: Shuying
authors: S
authors: Wu
authors: Vay Liang W
authors: VL
authors: Go
authors: Natalie
authors: N
authors: Toy
authors: Hong
authors: H
authors: Yang
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology; D007003:Hypoglycemia / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos