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Novel metabolic role for skeletal muscle BDNF in pancreatic β-cell insulin secretion
Fulgenzi, Gianluca NCI, National Institutes of Health
BDNF signaling in neuronal hypothalamic circuitries regulates mammalian food intake. Whether BDNF signaling exerts metabolic effects on peripheral organs is currently unclear. We found that the BDNF receptor TrkB.T1 is expressed by pancreatic β-cells where it regulates insulin release. Consequently, mice lacking this receptor show impaired glucose tolerance and insulin secretion. BDNF binding to β-cells TrkB.T1 triggers calcium release from intracellular stores, increasing glucose-induced insulin secretion. In addition, BDNF is secreted by skeletal muscle and knocking out BDNF in skeletal muscle of mice phenocopies the metabolic impairments caused by TrkB.T1 deletion in β-cells. The finding that BDNF is also secreted by differentiated human muscle cells and that it induces insulin secretion in human islets via TrkB.T1 identifies a new unexpected regulatory function of BDNF on metabolism that is independent of CNS activity. Our data suggest that muscle derived BDNF may be a key factor mediating increased glucose metabolism in response to exercise, with implications for the treatment of diabetes and related metabolic diseases.