title: Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve.
abstract: It is hypothesized that the vagus nerve makes a major contribution to pancreatic insulin hypersecretion in the genetically obese rat (fa/fa) via direct pancreatic innervation. An in situ brain-pancreas perfusion model with intact pancreatic central nervous system (CNS) innervation was used in these studies. The dynamics of insulin secretion in response to a 40-min glucose stimulus (200 mg/dl) was investigated in CNS intact (INT), bilateral cervical vagotomized (VGX), and CNS functionally ablated (ABL) 11- to 12-wk-old homozygous lean (Fa/Fa) and obese (fa/fa) female Zucker rats. The overall pattern of insulin secretory dynamics from obese and lean rats was similar. However, insulin released during the entire 40-min perfusion period by pancreata from obese rats was significantly greater than in lean rats. In lean rats, there was no significant difference in insulin secretion from pancreata of CNS-INT, VGX, and ABL rats. In obese rats, CNS-INT pancreata secreted almost twice as much insulin as pancreata from obese ABL rats and four times as much insulin as CNS-INT lean rats. This demonstrates that hypersecretion of insulin in obese Zucker rats is comprised of a significant direct CNS component. Although vagotomy had little effect on CNS-INT lean rats, it reversed the CNS component of hypersecretion present in CNS-INT obese rats. Because insulin secretion in CNS-INT obese rats was lowered by vagotomy to that equivalent to values of CNS-ABL obese rats, this demonstrates a significant contribution by the parasympathetic nervous system to the hyperinsulinemia seen in the Zucker obese rat that is attributed to direct parasympathetic innervation of the pancreas.
authors.affiliation: Department of Nutrition, College of Agricultural and Environmental Sciences, California.
authors.forename: H C
authors.initials: HC
authors.lastname: Lee
authors.forename: D L
authors.initials: DL
authors.lastname: Curry
authors.forename: J S
authors.initials: JS
authors.lastname: Stern
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D003433:Crosses, Genetic; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011922:Rats, Mutant Strains / Q000502:physiology*; D011924:Rats, Zucker / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D007328:Insulin