Kim Joong Kwan, Lim Yongchul, Lee Jung Ok, Lee Young-Sun, Won Nam Hee, Kim Hyun, Kim Hyeon Soo
Department of AnatomyKorea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-701, KoreaDepartment of SurgerySamsung Medical Center, 81, Irwon-Ro, Gangnam-Gu, Seoul 135-710, KoreaDepartment of PathologyKorea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-701, KoreaLee Gil Ya Cancer and Diabetes InstituteGachon University, Inchon, Kyunggi do, Korea.
Department of AnatomyKorea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-701, KoreaDepartment of SurgerySamsung Medical Center, 81, Irwon-Ro, Gangnam-Gu, Seoul 135-710, KoreaDepartment of PathologyKorea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-701, KoreaLee Gil Ya Cancer and Diabetes InstituteGachon University, Inchon, Kyunggi do, Korea
J Mol Endocrinol. 2015 Jun;54(3):315-24. doi: 10.1530/JME-14-0325. Epub 2015 Apr 27.
The relationship between protein arginine methyltransferases (PRMTs) and insulin synthesis in β cells is not yet well understood. In the present study, we showed that PRMT4 expression was increased in INS-1 and HIT-T15 pancreatic β cells under high-glucose conditions. In addition, asymmetric dimethylation of Arg17 in histone H3 was significantly increased in both cell lines in the presence of glucose. The inhibition or knockdown of PRMT4 suppressed glucose-induced insulin gene expression in INS-1 cells by 81.6 and 79% respectively. Additionally, the overexpression of mutant PRMT4 also significantly repressed insulin gene expression. Consistently, insulin secretion induced in response to high levels of glucose was decreased by both PRMT4 inhibition and knockdown. Moreover, the inhibition of PRMT4 blocked high-glucose-induced insulin gene expression and insulin secretion in primary pancreatic islets. These results indicate that PRMT4 might be a key regulator of high-glucose-induced insulin secretion from pancreatic β cells via H3R17 methylation.
蛋白质精氨酸甲基转移酶（PRMTs）与β细胞中胰岛素合成之间的关系尚未完全明确。在本研究中，我们发现，在高糖条件下，INS-1和HIT-T15胰腺β细胞中PRMT4的表达增加。此外，在葡萄糖存在的情况下，两种细胞系中组蛋白H3的精氨酸17位点的不对称二甲基化均显著增加。PRMT4的抑制或敲低分别使INS-1细胞中葡萄糖诱导的胰岛素基因表达降低了81.6%和79%。此外，突变型PRMT4的过表达也显著抑制了胰岛素基因表达。同样，PRMT4的抑制和敲低均降低了对高水平葡萄糖诱导的胰岛素分泌。此外，PRMT4的抑制阻断了原代胰岛中高糖诱导的胰岛素基因表达和胰岛素分泌。这些结果表明，PRMT4可能是通过H3R17甲基化调控高糖诱导的胰腺β细胞胰岛素分泌的关键调节因子。
