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Hypothalamic Brain‐Derived Neurotrophic Factor Regulates Glucagon Secretion Mediated by Pancreatic Efferent Nerves
Author(s) -
Gotoh K.,
Masaki T.,
Chiba S.,
Ando H.,
Fujiwara K.,
Shimasaki T.,
Mitsutomi K.,
Katsuragi I.,
Kakuma T.,
Sakata T.,
Yoshimatsu H.
Publication year - 2013
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12003
Subject(s) - endocrinology , medicine , glucagon , neurotrophic factors , efferent , insulin , central nervous system , hypothalamus , brain derived neurotrophic factor , biology , receptor , afferent
Understanding the molecular mechanism of the regulation of glucagon secretion is critical for treating the dysfunction of α 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 α 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 α 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 α cells were stained specifically with BDNF and tyrosine‐related kinase B, a specific receptor for BDNF , and α 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 α cells via the central and peripheral nervous systems.