PMID- 28717164
OWN - NLM
STAT- MEDLINE
DCOM- 20190220
LR  - 20190320
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 17
TI  - Glucagon-like peptide-1 reduces pancreatic beta-cell mass through hypothalamic 
      neural pathways in high-fat diet-induced obese rats.
PG  - 5578
LID - 10.1038/s41598-017-05371-4 [doi]
LID - 5578
AB  - We examined whether glucagon-like peptide-1 (GLP-1) affects beta-cell mass and 
      proliferation through neural pathways, from hepatic afferent nerves to pancreatic 
      efferent nerves via the central nervous system, in high-fat diet (HFD)-induced 
      obese rats. The effects of chronic administration of GLP-1 (7-36) and 
      liraglutide, a GLP-1 receptor agonist, on pancreatic morphological alterations, 
      c-fos expression and brain-derived neurotrophic factor (BDNF) content in the 
      hypothalamus, and glucose metabolism were investigated in HFD-induced obese rats 
      that underwent hepatic afferent vagotomy (VgX) and/or pancreatic efferent 
      sympathectomy (SpX). Chronic GLP-1 (7-36) administration to HFD-induced obese 
      rats elevated c-fos expression and BDNF content in the hypothalamus, followed by 
      a reduction in pancreatic beta-cell hyperplasia and insulin content, thus resulting 
      in improved glucose tolerance. These responses were abolished by VgX and SpX. 
      Moreover, administration of liraglutide similarly activated the hypothalamic 
      neural pathways, thus resulting in a more profound amelioration of glucose 
      tolerance than native GLP-1 (7-36). These data suggest that GLP-1 normalizes the 
      obesity-induced compensatory increase in beta-cell mass and glucose intolerance 
      through a neuronal relay system consisting of hepatic afferent nerves, the 
      hypothalamus, and pancreatic efferent nerves.
FAU - Ando, Hisae
AU  - Ando H
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
FAU - Gotoh, Koro
AU  - Gotoh K
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan. 
      gotokoro@oita-u.ac.jp.
FAU - Fujiwara, Kansuke
AU  - Fujiwara K
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
FAU - Anai, Manabu
AU  - Anai M
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
FAU - Chiba, Seiichi
AU  - Chiba S
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
FAU - Masaki, Takayuki
AU  - Masaki T
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
FAU - Kakuma, Tetsuya
AU  - Kakuma T
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
FAU - Shibata, Hirotaka
AU  - Shibata H
AD  - Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of 
      Medicine, Oita University, Yufu city, Oita, 879-5593, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170717
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 839I73S42A (Liraglutide)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cell Size/drug effects
MH  - Diet, High-Fat/*adverse effects
MH  - Glucagon-Like Peptide 1/*administration & dosage/pharmacology
MH  - Glucose/metabolism
MH  - Glucose Intolerance/drug therapy/etiology
MH  - Hypothalamus/drug effects/*metabolism
MH  - Injections, Intraperitoneal
MH  - Insulin-Secreting Cells/*cytology/drug effects/metabolism
MH  - Liraglutide/administration & dosage/pharmacology
MH  - Neural Pathways/*drug effects
MH  - Obesity/chemically induced/*drug therapy/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sympathectomy
MH  - Vagotomy
PMC - PMC5514038
COIS- The authors declare that they have no competing interests.
EDAT- 2017/07/19 06:00
MHDA- 2019/03/21 06:00
PMCR- 2017/07/17
CRDT- 2017/07/19 06:00
PHST- 2016/10/03 00:00 [received]
PHST- 2017/05/30 00:00 [accepted]
PHST- 2017/07/19 06:00 [entrez]
PHST- 2017/07/19 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2017/07/17 00:00 [pmc-release]
AID - 10.1038/s41598-017-05371-4 [pii]
AID - 5371 [pii]
AID - 10.1038/s41598-017-05371-4 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 17;7(1):5578. doi: 10.1038/s41598-017-05371-4.