| First Author | Yamamotoya T | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 13026 |
| PubMed ID | 29026155 | Mgi Jnum | J:256557 |
| Mgi Id | MGI:6109551 | Doi | 10.1038/s41598-017-13432-x |
| Citation | Yamamotoya T, et al. (2017) Trk-fused gene (TFG) regulates pancreatic beta cell mass and insulin secretory activity. Sci Rep 7(1):13026 |
| abstractText | The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, beta-cell specific TFG knockout mice (betaTFG KO) were generated. Interestingly, betaTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller beta-cell masses in betaTFG KO than in controls, likely attributable to diminished beta-cell proliferation. Consistently, beta-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in betaTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from betaTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in beta-cells of betaTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic beta-cells plays a vital role in maintaining both the mass and function of beta-cells, and its dysfunction increases the tendency to develop glucose intolerance. |
