Neuronal activation of brain vagal-regulatory pathways and upper gut enteric plexuses by insulin hypoglycemia.
Neuronal activation of brain vagal-regulatory nuclei and gastric/duodenal enteric plexuses in response to insulin (2 U/kg, 2 h) hypoglycemia was studied in rats. Insulin hypoglycemia significantly induced Fos expression in the paraventricular nucleus of the hypothalamus, locus coeruleus, dorsal motor nucleus of the vagus (DMN), and nucleus tractus solitarii (NTS), as well as in the gastric/duodenal myenteric/submucosal plexuses. A substantial number of insulin hypoglycemia-activated DMN and NTS neurons were choline acetyltransferase and tyrosine hydroxylase positive, respectively, whereas the activated enteric neurons included NADPH- and vasoactive intestinal peptide neurons. The numbers of Fos-positive cells in each above-named brain nucleus or in the gastric/duodenal myenteric plexus of insulin-treated rats were negatively correlated with serum glucose levels and significantly increased when glucose levels were lower than 80 mg/dl. Acute bilateral cervical vagotomy did not influence insulin hypoglycemia-induced Fos induction in the brain vagal-regulatory nuclei but completely and partially prevented this response in the gastric and duodenal enteric plexuses, respectively. These results revealed that brain-gut neurons regulating vagal outflow to the stomach/duodenum are sensitively responsive to insulin hypoglycemia.
Yuan
Pu-Qing
PQ
Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine, Division of Digestive Diseases and Brain Research Institute, University of California, Los Angeles, Los Angeles, California 90073, USA.
Yang
Hong
H
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D004386:Duodenum / Q000294:innervation; D017615:Enteric Nervous System / Q000378:metabolism / Q000503:physiopathology*; D005724:Ganglia / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007004:Hypoglycemic Agents; D007328:Insulin; D008297:Male; D009249:NADP / Q000378:metabolism; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000294:innervation; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000503:physiopathology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D016760:Proto-Oncogene Proteins c-fos; D014660:Vasoactive Intestinal Peptide; D009249:NADP; D014446:Tyrosine 3-Monooxygenase