| First Author | Liu J | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1865 |
| Issue | 9 | Pages | 2138-2148 |
| PubMed ID | 31029827 | Mgi Jnum | J:282118 |
| Mgi Id | MGI:6323836 | Doi | 10.1016/j.bbadis.2019.04.011 |
| Citation | Liu J, et al. (2019) METTL14 is essential for beta-cell survival and insulin secretion. Biochim Biophys Acta Mol Basis Dis 1865(9):2138-2148 |
| abstractText | Defects in the development, maintenance or expansion of beta-cell mass can result in impaired glucose metabolism and diabetes. N(6)-methyladenosine affects mRNA stability and translation efficiency, and impacts cell differentiation and stress response. To determine if there is a role for m(6)A in beta-cells, we investigated the effect of Mettl14, a key component of the m(6)A methyltransferase complex, on beta-cell survival and function using rat insulin-2 promoter-Cre-mediated deletion of Mettl14 mouse line (betaKO). We found that betaKO mice with normal chow exhibited glucose intolerance, lower levels of glucose-stimulated insulin secretion, increased beta-cell death and decreased beta-cell mass. In addition, HFD-fed betaKO mice developed glucose intolerance, decreased beta-cell mass and proliferation, exhibited lower body weight, increased adipose tissue mass, and enhanced insulin sensitivity due to enhanced AKT signaling and decreased gluconeogenesis in the liver. HFD-fed betaKO mice also showed a decrease in de novo lipogenesis, and an increase in lipolysis in the liver. RNA sequencing in islets revealed that Mettl14 deficiency in beta-cells altered mRNA expression levels of some genes related to cell death and inflammation. Together, we showed that Mettl14 in beta-cells plays a key role in beta-cell survival, insulin secretion and glucose homeostasis. |
