| First Author | Men L | Year | 2019 |
| Journal | Endocrinology | Volume | 160 |
| Issue | 10 | Pages | 2388-2394 |
| PubMed ID | 31369074 | Mgi Jnum | J:287821 |
| Mgi Id | MGI:6363900 | Doi | 10.1210/en.2019-00350 |
| Citation | Men L, et al. (2019) Acute Deletion of METTL14 in beta-Cells of Adult Mice Results in Glucose Intolerance. Endocrinology 160(10):2388-2394 |
| abstractText | N6-Methyladenosine (m6A) is the most common and abundant mRNA modification that involves regulating the RNA metabolism. However, the role of m6A in regulating the beta-cell function is unclear. Methyltransferase-like 14 (METTL14) is a key component of the m6A methyltransferase complex. To define the role of m6A in regulating the beta-cell function, we generated beta-cell METTL14-specific knockout (betaKO) mice by tamoxifen administration. Acute deletion of Mettl14 in beta-cells results in glucose intolerance as a result of a reduction in insulin secretion in beta-cells even though beta-cell mass is increased, which is related to increased beta-cell proliferation. To define the molecular mechanism, we performed RNA sequencing to detect the gene expression in betaKO islets. The genes responsible for endoplasmic reticulum stress, such as Ire1alpha, were among the top upregulated genes. Both mRNA and protein levels of IRE1alpha and spliced X-box protein binding 1 (sXBP-1) were increased in betaKO islets. The protein levels of proinsulin and insulin were decreased in betaKO islets. These results suggest that acute METTL14 deficiency in beta-cells induces glucose intolerance by increasing the IRE1alpha/sXBP-1 pathway. |
