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Exenatide and feeding: possible peripheral neuronal pathways.

Jizette V Hunt1, Martha C Washington, Ayman I Sayegh

  • 1Gastroenterology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088, United States.

Peptides
|January 7, 2012
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Summary

Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces food intake via vagal and splanchnic nerves. These nerves are crucial for exenatide

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Published on: August 24, 2016

Area of Science:

  • Neuroscience
  • Endocrinology
  • Gastroenterology

Background:

  • Glucagon-like peptide-1 (GLP-1) receptor agonists, like exenatide, are used to manage type 2 diabetes and obesity.
  • Exenatide administered intraperitoneally (i.p.) is known to reduce food intake.
  • The peripheral neural pathways mediating exenatide's anorectic effects remain incompletely understood.

Purpose of the Study:

  • To investigate the roles of the vagus nerve and splanchnic nerves in mediating exenatide-induced reduction of food intake.
  • To determine if specific nerve pathways are differentially involved in the effects of exenatide on meal size and intermeal interval.

Main Methods:

  • Adult male rats were subjected to overnight food deprivation.
  • Surgical procedures included total subdiaphragmatic vagotomy (VGX), celiacomesenteric ganglionectomy (CMGX), or combined VGX/CMGX.
  • Exenatide (0.5 μg/kg, i.p.) was administered, and subsequent meal sizes (MSs) and intermeal intervals (IMIs) were recorded for 120 minutes.

Main Results:

  • Exenatide reduced the size of the first two meals but did not prolong the intermeal interval.
  • Vagotomy (VGX) attenuated the reduction in the first meal size induced by exenatide.
  • Both vagotomy (VGX) and celiacomesenteric ganglionectomy (CMGX), individually or combined, attenuated the reduction in the second meal size by exenatide.

Conclusions:

  • The vagus nerve is essential for exenatide's effect on the first meal size.
  • Both the vagus nerve and splanchnic nerves are necessary for exenatide's effect on the second meal size.
  • Peripheral neural pathways, particularly the vagus and splanchnic nerves, play critical roles in mediating the anorectic effects of exenatide.