AJP - Endocrinology and Metabolism, Vol 256, Issue 3 E439-E444, Copyright © 1989 by American Physiological Society
Direct effect of CNS on insulin hypersecretion in obese Zucker rats: involvement of vagus nerve
H. C. Lee, D. L. Curry and J. S. Stern
Department of Nutrition, College of Agricultural and Environmental Sciences, California.
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.
