| First Author | Altman MK | Year | 2021 |
| Journal | Development | Volume | 148 |
| Issue | 16 | PubMed ID | 34345920 |
| Mgi Jnum | J:339816 | Mgi Id | MGI:6754049 |
| Doi | 10.1242/dev.194928 | Citation | Altman MK, et al. (2021) TRPM7 is a crucial regulator of pancreatic endocrine development and high-fat-diet-induced beta-cell proliferation. Development 148(16):dev194928 |
| abstractText | The melastatin subfamily of the transient receptor potential channels (TRPM) are regulators of pancreatic beta-cell function. TRPM7 is the most abundant islet TRPM channel; however, the role of TRPM7 in beta-cell function has not been determined. Here, we used various spatiotemporal transgenic mouse models to investigate how TRPM7 knockout influences pancreatic endocrine development, proliferation and function. Ablation of TRPM7 within pancreatic progenitors reduced pancreatic size, and alpha-cell and beta-cell mass. This resulted in modestly impaired glucose tolerance. However, TRPM7 ablation following endocrine specification or in adult mice did not impact endocrine expansion or glucose tolerance. As TRPM7 regulates cell proliferation, we assessed how TRPM7 influences beta-cell hyperplasia under insulin-resistant conditions. beta-Cell proliferation induced by high-fat diet was significantly decreased in TRPM7-deficient beta-cells. The endocrine roles of TRPM7 may be influenced by cation flux through the channel, and indeed we found that TRPM7 ablation altered beta-cell Mg2+ and reduced the magnitude of elevation in beta-cell Mg2+ during proliferation. Together, these findings revealed that TRPM7 controls pancreatic development and beta-cell proliferation, which is likely due to regulation of Mg2+ homeostasis. |
