The role of central glucagon-like peptide-1 in mediating the effects of visceral illness: Differential effects in rats and mice

Jennifer L. Lachey, David A. D'Alessio, Linda Rinaman, Joel K. Elmquist, Daniel J. Drucker, Randy J. Seeley

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

In rats, central administration of glucagon-like peptide-1 (GLP-1) elicits symptoms of visceral illness like those caused by the toxin lithium chloride (LiCl), including anorexia, conditioned taste aversion (CTA) formation, and neural activation in the hypothalamus and hindbrain including activation of brainstem preproglucagon cells. Most compellingly, pharmacological antagonists of the GLP-1 receptor (GLP-1R) block several effects of LiCl in rat. The major goal of these experiments was to further test the hypothesis that the central nervous system GLP-1 system is critical to the visceral illness actions of LiCl by using mice with a targeted disruption of the only described GLP-1R. First, we observed that, like the rat, LiCl activates preproglucagon neurons in wild-type mice. Second, GLP-1R -/- mice demonstrated normal anorexic and CTA responses to LiCl. To test the possibility that alternate GLP-1Rs mediate aversive effects, we examined the ability of GLP-1 to produce a CTA in GLP1R -/- mice. Although lateral ventricular GLP-1 produced a CTA in wild-type mice, it did not produce a CTA in GLP-1R -/- mice. Furthermore, the same GLP-1R antagonist that can block the aversive effects of LiCl in the rat failed to do so in the mouse. These results support the conclusion that in mouse, unlike in rat, GLP-1R signaling is not required for the visceral illness response to LiCl. Such species differences are an important consideration when comparing results from rat and mouse studies.

Original languageEnglish (US)
Pages (from-to)458-462
Number of pages5
JournalEndocrinology
Volume146
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Glucagon-Like Peptide 1
Lithium Chloride
Proglucagon
Rhombencephalon
Aptitude
Anorexia
Hypothalamus
Brain Stem
Glucagon-Like Peptide-1 Receptor
Central Nervous System
Pharmacology
Neurons

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The role of central glucagon-like peptide-1 in mediating the effects of visceral illness : Differential effects in rats and mice. / Lachey, Jennifer L.; D'Alessio, David A.; Rinaman, Linda; Elmquist, Joel K.; Drucker, Daniel J.; Seeley, Randy J.

In: Endocrinology, Vol. 146, No. 1, 01.2005, p. 458-462.

Research output: Contribution to journalArticle

Lachey, Jennifer L. ; D'Alessio, David A. ; Rinaman, Linda ; Elmquist, Joel K. ; Drucker, Daniel J. ; Seeley, Randy J. / The role of central glucagon-like peptide-1 in mediating the effects of visceral illness : Differential effects in rats and mice. In: Endocrinology. 2005 ; Vol. 146, No. 1. pp. 458-462.
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