Novel metabolic role for BDNF in pancreatic β-cell insulin secretion

• Published in: Nature communications Vol. 11; no. 1; p. 1950
• Main Authors: Fulgenzi, Gianluca, Hong, Zhenyi, Tomassoni-Ardori, Francesco, Barella, Luiz F., Becker, Jodi, Barrick, Colleen, Swing, Deborah, Yanpallewar, Sudhirkumar, Croix, Brad St, Wess, Jürgen, Gavrilova, Oksana, Tessarollo, Lino
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.04.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/106; 631/80/86/2367; 64/110; 64/60; 692/698/1671/1668/1973; 692/698/2741/416; 96/95; Animals; Beta cells; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium signalling; Cell differentiation; Cells, Cultured; Clonal deletion; Diabetes mellitus; Food intake; Glucose; Glucose - metabolism; Glucose Intolerance; Glucose tolerance; Humanities and Social Sciences; Humans; Hypothalamus; Insulin; Insulin Secretion; Insulin-Secreting Cells - metabolism; Intracellular signalling; Islets of Langerhans - metabolism; Male; Medical treatment; Metabolic disorders; Metabolism; Mice; Mice, Knockout; multidisciplinary; Muscle Fibers, Skeletal - metabolism; Muscles; Organs; Pancreas; Protein Isoforms - genetics; Protein Isoforms - metabolism; Receptor, trkB - chemistry; Receptor, trkB - genetics; Receptor, trkB - metabolism; Science; Science (multidisciplinary); Secretion; Signal Transduction; Signaling; Skeletal muscle; TrkB receptors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15833-5

BDNF signaling in hypothalamic circuitries regulates mammalian food intake. However, whether BDNF exerts metabolic effects on peripheral organs is currently unknown. Here, we show that the BDNF receptor TrkB.T1 is expressed by pancreatic β-cells where it regulates insulin release. Mice lacking TrkB.T1 show impaired glucose tolerance and insulin secretion. β-cell BDNF-TrkB.T1 signaling triggers calcium release from intracellular stores, increasing glucose-induced insulin secretion. Additionally, BDNF is secreted by skeletal muscle and muscle-specific BDNF knockout phenocopies the β-cell TrkB.T1 deletion metabolic impairments. The finding that BDNF is also secreted by differentiated human muscle cells and induces insulin secretion in human islets via TrkB.T1 identifies a new 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. Glucose metabolism is regulated by hypothalamic brain functions and factors produced by peripheral tissues. Here, the authors show that the regulator of food intake Brain-derived neurotrophic factor is also produced and secreted by muscle and stimulates pancreas insulin release.