2026-03-16T00:20:52Z https://kumadai.repo.nii.ac.jp/oai

oai:kumadai.repo.nii.ac.jp:00026636 2023-06-19T17:48:49Z 413:443

Development of type 2 diabetes caused by a deficiency of a tRNAlys modification 魏, 范研 富澤, 一仁 Wei, Fan-Yan Tomizawa, Kazuhito © 2012 Landes Bioscience 493 Cdkal1 ER stress Islet Translation tRNA application/pdf 論文(Article) Genetic variations in the cdk5 regulator associated protein 1-like 1 (cdkal1) gene have been identified in whole genome association studies as a risk factor for the development of type 2 diabetes (T2D). A recent study showed that Cdkal1 was a mammalian methythiotransferase, which specifically synthesizes 2-methylthio-N 6-threonylcarbamoyladenosine (ms 2t 6A) at position 37 of tRNA lys(UUU). The ms 2t 6A modification in tRNA lys(UUU) was important for the accurate decoding of its cognate codon. In pancreatic β-cell-specific Cdkal1 knockout (Cdkal1 KO) mice, a deficiency of ms 2t 6A caused the mistranslation of a Lys codon in proinsulin, resulting in improper processing. The mice showed a decrease in insulin secretion and glucose intolerance. In addition, the mistranslation contributed to the expression of the endoplasmic reticulum (ER) stress response in Cdkal1-deficient β-cells. Furthermore, Cdkal1 KO mice were hypersensitive to high-fat diet-induced glucose intolerance, as well as the ER stress response. These findings might potentially explain the molecular pathogenesis of T2D in patients carrying Cdkal1 variations. http://www.landesbioscience.com/journals/islets/article/18262/ Landes Bioscience 2012-01 eng journal article AM http://hdl.handle.net/2298/25749 https://kumadai.repo.nii.ac.jp/records/26636 10.4161/isl.18262 19382014 Islets 4 1 71 73 https://kumadai.repo.nii.ac.jp/record/26636/files/Islets,4,1,71-73.pdf application/pdf 74.9 kB 2020-03-02