PRMT4 is involved in insulin secretion via the methylation of histone H3 in pancreatic β cells.
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.
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.
Joong Kwan
JK
Kim
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.
Yongchul
Y
Lim
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.
Jung Ok
JO
Lee
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.
Young-Sun
YS
Lee
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.
Nam Hee
NH
Won
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.
Hyun
H
Kim
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 anatomykim@korea.ac.kr.
Hyeon Soo
HS
Kim
D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D004790:Enzyme Induction; D005947:Glucose / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D051381:Rats
D006657:Histones; D007328:Insulin; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D005947:Glucose
PRMT4; histone H3R17; insulin secretion; insulin synthesis