Direct effect of CNS on insulin hypersecretion in obese Zucker rats: Involvement of vagus nerve

H. C. Lee, D. L. Curry, J. S. Stern

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38 Scopus citations


It is hypothesized that the vagus nerve makes a major contribution to pancreatic insulin hypersecretion in the genetically obese rate (fa/fa) via direct pancreatric 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number3
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology


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