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On-target effects of GLP-1 receptor agonists on thyroid C-cells in rats and mice

Thomas J Rosol1

  • 1The Ohio State University, Department of Veterinary Biosciences, Columbus, Ohio 43210, USA. rosol.1@osu.edu

Toxicologic Pathology
|March 9, 2013
PubMed

Insights

Glucagon-like peptide-1 (GLP-1) receptor agonists, used for type 2 diabetes, may cause C-cell hyperplasia in rodents. However, this effect appears rodent-specific and may not apply to humans due to differing GLP-1 receptor presence.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Gastroenterology

Background:

  • Glucagon-like peptide-1 (GLP-1) is an incretin hormone regulating glucose homeostasis.
  • GLP-1 receptor agonists are a therapeutic class for Type 2 Diabetes Mellitus.
  • Clinical GLP-1 analogues feature prolonged half-lives due to rapid degradation by dipeptidyl peptidase IV.

Purpose of the Study:

  • To investigate the effects of GLP-1 receptor agonists on C-cell proliferation and neoplasia.
  • To determine the species-specificity of GLP-1 agonist-induced C-cell effects.

Main Methods:

  • Review of studies on GLP-1 receptor agonists, including exenatide and liraglutide.
  • Analysis of findings regarding calcitonin secretion, C-cell hyperplasia, and neoplasia in rodents.
  • Comparison of GLP-1 receptor expression in C-cells across different species (rodents, nonhuman primates, humans).

Main Results:

  • GLP-1 receptor agonists increase calcitonin secretion and stimulate C-cell hyperplasia and neoplasia in rodents.
  • Rodent C-cells exhibit higher sensitivity to GLP-1 agonists compared to other species.
  • GLP-1 receptors are present on rodent C-cells but absent or in low numbers on nonhuman primate and human C-cells.

Conclusions:

  • The observed C-cell hyperplasia and neoplasia in rodents treated with GLP-1 agonists is a species-specific effect.
  • This rodent-specific effect is likely mediated by the presence of GLP-1 receptors on rodent C-cells.
  • The findings suggest that the proliferative C-cell effects of GLP-1 agonists may not be relevant to humans.

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