Journal
JOURNAL OF NEUROENDOCRINOLOGY
Volume 25, Issue 3, Pages 302-311Publisher
WILEY-BLACKWELL
DOI: 10.1111/jne.12003
Keywords
brain-derived neurotrophic factor; GLP-1; hypothalamus; glucagon; pancreatic efferent nerve
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Funding
- Japan's Ministry of Health, Labor, and Welfare
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Understanding the molecular mechanism of the regulation of glucagon secretion is critical for treating the dysfunction of 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 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 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 cells were stained specifically with BDNF and tyrosine-related kinase B, a specific receptor for BDNF, and 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 cells via the central and peripheral nervous systems.
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