PMID- 23157205
OWN - NLM
STAT- MEDLINE
DCOM- 20130812
LR  - 20181202
IS  - 1365-2826 (Electronic)
IS  - 0953-8194 (Linking)
VI  - 25
IP  - 3
DP  - 2013 Mar
TI  - Hypothalamic brain-derived neurotrophic factor regulates glucagon secretion 
      mediated by pancreatic efferent nerves.
PG  - 302-11
LID - 10.1111/jne.12003 [doi]
AB  - Understanding the molecular mechanism of the regulation of glucagon secretion is 
      critical for treating the dysfunction of alpha cells observed in diabetes. 
      Glucagon-like peptide (GLP)-1 analogues reduce plasma glucagon and are assumed to 
      contribute to their action to lower blood glucose. It has previously been 
      demonstrated that the central administration of brain-derived neurotrophic factor 
      (BDNF) improves glucose metabolism by a mechanism independent of feeding 
      behaviour in obese subjects. Using male rats, we examined whether BDNF influences 
      glucagon secretion from alpha cells via the the central nervous system. We 
      investigate whether: (i) the central infusion of BDNF stimulates glucagon and/or 
      insulin secretion via the pancreatic efferent nerve from the hypothalamus; (ii) 
      the intraportal infusion of GLP-1 regulates glucose metabolism via the central 
      and peripheral nervous system; and (iii) BDNF receptor and/or BDNF-positive 
      fibres are localised near alpha cells of islets. The portal glucagon level decreased 
      with the central administration of BDNF (n = 6, in each; P < 0.05); in contrast, 
      there was no significant change in portal insulin, peripheral glucagon and 
      insulin levels with the same treatment. This reduction of glucagon secretion was 
      abolished by pancreatic efferent denervation (n = 6, in each; P < 0.05). In an 
      immunohistochemical study, pancreatic alpha cells were stained specifically with BDNF 
      and tyrosine-related kinase B, a specific receptor for BDNF, and alpha cells were 
      also co-localised with BDNF. Moreover, intraportal administration of GLP-1 
      decreased glucagon secretion, as well as blood glucose, whereas it increased the 
      BDNF content in the pancreas; these effects were inhibited with the central 
      infusion of BDNF antibody (n = 6, in each; P < 0.05). BDNF and GLP-1 affect 
      glucose metabolism and modulate glucagon secretion from pancreatic alpha cells via 
      the central and peripheral nervous systems.
CI  - (c) 2012 British Society for Neuroendocrinology.
FAU - Gotoh, K
AU  - Gotoh K
AD  - Department of Internal Medicine 1, Faculty of Medicine, Oita University, Yufu, 
      Japan. gotokoro@oita-u.ac.jp
FAU - Masaki, T
AU  - Masaki T
FAU - Chiba, S
AU  - Chiba S
FAU - Ando, H
AU  - Ando H
FAU - Fujiwara, K
AU  - Fujiwara K
FAU - Shimasaki, T
AU  - Shimasaki T
FAU - Mitsutomi, K
AU  - Mitsutomi K
FAU - Katsuragi, I
AU  - Katsuragi I
FAU - Kakuma, T
AU  - Kakuma T
FAU - Sakata, T
AU  - Sakata T
FAU - Yoshimatsu, H
AU  - Yoshimatsu H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neuroendocrinol
JT  - Journal of neuroendocrinology
JID - 8913461
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Insulin)
RN  - 89750-14-1 (Glucagon-Like Peptide 1)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - *Efferent Pathways
MH  - Glucagon/*metabolism
MH  - Glucagon-Like Peptide 1/metabolism
MH  - Glucose Tolerance Test
MH  - Hypothalamus/*metabolism
MH  - Immunohistochemistry
MH  - Insulin/metabolism
MH  - Male
MH  - Pancreas/*innervation
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2012/11/20 06:00
MHDA- 2013/08/13 06:00
CRDT- 2012/11/20 06:00
PHST- 2012/06/26 00:00 [received]
PHST- 2012/10/18 00:00 [revised]
PHST- 2012/11/10 00:00 [accepted]
PHST- 2012/11/20 06:00 [entrez]
PHST- 2012/11/20 06:00 [pubmed]
PHST- 2013/08/13 06:00 [medline]
AID - 10.1111/jne.12003 [doi]
PST - ppublish
SO  - J Neuroendocrinol. 2013 Mar;25(3):302-11. doi: 10.1111/jne.12003.