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Central administration of GLP-1 and GIP decreases feeding in mice.

Abstract
Glucagon-like peptide-1 amide (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones regulating energy metabolism. GLP-1 and GIP combination is suggested as a promising therapeutic strategy for treatment of obesity and diabetes. However, the neuronal mechanisms are not yet investigated. In the present study, we investigated the role of central GLP-1 and GIP in regulation of body weight homeostasis. The effect of GLP-1 with GIP on food intake, body weight, locomotor activity were determined following intracerebroventricular (ICV) administration of GLP-1 and/or GIP in mice. ICV administration of low dose GLP-1 (0.3 nmol) and GIP (1 and 3 nmol) did not change food intake. However, ICV administration of higher doses GLP-1 (1 and 3 nmol) and GIP (6 nmol) significantly decreased food intake and body weight. To investigate the synergic effect of ICV GLP-1 and GIP, subeffective dose GLP-1 (0.3 nmol) and subeffective dose GIP (1 nmol) were chosen for further co-administration study. ICV co-administration of GLP-1 and GIP significantly decreased food intake, body weight and drinking. ICV co-administration of GLP-1 and GIP significantly increased neuronal activation and pro-opiomelanocortin (POMC) expression in hypothalamic arcuate nucleus. The neuronal activation and POMC expression were observed in two distinct neuronal populations. These results provide neuronal mechanisms supporting the development of GLP-1 and GIP combination therapeutics for treatment of obesity and diabetes.
AuthorsCherl NamKoong, Min Sun Kim, Byeong-Tak Jang, Young Hee Lee, Young-Min Cho, Hyung Jin Choi
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 490 Issue 2 Pg. 247-252 (08 19 2017) ISSN: 1090-2104 [Electronic] United States
PMID28610922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
Topics
  • Animals
  • Eating (drug effects)
  • Gastric Inhibitory Polypeptide (administration & dosage, pharmacology)
  • Glucagon-Like Peptide 1 (administration & dosage, pharmacology)
  • Infusions, Intraventricular
  • Male
  • Mice
  • Mice, Inbred C57BL

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