Novel metabolic role for BDNF in pancreatic β-cell insulin secretion.
Gianluca FulgenziZhenyi HongFrancesco Tomassoni-ArdoriLuiz Felipe BarellaJodi BeckerColleen BarrickDeborah SwingSudhirkumar YanpallewarBrad St CroixJürgen WessOksana GavrilovaLino TessarolloPublished in: Nature communications (2020)
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.
Keyphrases
- stress induced
- skeletal muscle
- type diabetes
- endothelial cells
- induced apoptosis
- cell therapy
- cardiovascular disease
- gene expression
- oxidative stress
- blood pressure
- metabolic syndrome
- insulin resistance
- cell cycle arrest
- body composition
- adipose tissue
- high intensity
- blood brain barrier
- artificial intelligence
- mesenchymal stem cells
- reactive oxygen species
- dna methylation
- replacement therapy