1. METTL14 is essential for β-cell survival and insulin secretion.
- Author
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Liu J, Luo G, Sun J, Men L, Ye H, He C, and Ren D
- Subjects
- Animals, Cell Survival, Diet, High-Fat, Gene Expression Regulation, Gluconeogenesis, Glucose Intolerance, Insulin metabolism, Insulin-Secreting Cells cytology, Insulin-Secreting Cells metabolism, Lipogenesis, Lithostathine genetics, Lithostathine metabolism, Liver metabolism, Liver pathology, Male, Methyltransferases antagonists & inhibitors, Methyltransferases genetics, Mice, Mice, Knockout, Pancreatitis-Associated Proteins genetics, Pancreatitis-Associated Proteins metabolism, Proto-Oncogene Proteins c-akt metabolism, RNA Interference, RNA, Small Interfering metabolism, Insulin Secretion, Methyltransferases metabolism
- Abstract
Defects in the development, maintenance or expansion of β-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 m6 A in β-cells, we investigated the effect of Mettl14, a key component of the m6 A methyltransferase complex, on β-cell survival and function using rat insulin-2 promoter-Cre-mediated deletion of Mettl14 mouse line (βKO). We found that βKO mice with normal chow exhibited glucose intolerance, lower levels of glucose-stimulated insulin secretion, increased β-cell death and decreased β-cell mass. In addition, HFD-fed βKO mice developed glucose intolerance, decreased β-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 βKO 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 β-cells altered mRNA expression levels of some genes related to cell death and inflammation. Together, we showed that Mettl14 in β-cells plays a key role in β-cell survival, insulin secretion and glucose homeostasis., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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