title: MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4.
abstract: Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients' plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3'UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.
authors.affiliation: Department of Geriatric Endocrinology, PLA General Hospital, Beijing, 100853, China.
authors.forename: Shuang-Tong
authors.initials: ST
authors.lastname: Yan
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Pei
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Gong
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Fang
authors.forename: Ban-Ruo
authors.initials: BR
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D051381:Rats
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D051275:Glucose Transporter Type 4; D035683:MicroRNAs; C495692:SLC2A4 protein, human; C531408:mirn199 microRNA, human; D005947:Glucose
references.citation: Nat Med. 1997 Oct;3(10):1096-101
references.pmid: 9334720
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8
references.pmid: 21383194
references.citation: PLoS One. 2009;4(5):e5532
references.pmid: 19440243
references.citation: Adv Exp Med Biol. 2013;774:1-20
references.pmid: 23377965
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4402-7
references.pmid: 19246379
references.citation: J Clin Endocrinol Metab. 1993 Jul;77(1):27-32
references.pmid: 8325952
references.citation: Curr Genomics. 2009 May;10(3):154-68
references.pmid: 19881909
references.citation: Clin Chem. 2009 Nov;55(11):1977-83
references.pmid: 19745058
references.citation: Am J Physiol. 1993 Dec;265(6 Pt 1):E889-97
references.pmid: 8279544
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8
references.pmid: 18663219
references.citation: Oncogene. 2013 Feb 21;32(8):976-87
references.pmid: 22469983
references.citation: Diabetes Care. 1990 Mar;13(3):198-208
references.pmid: 2407475
references.citation: Diabetes. 2001 Mar;50(3):593-600
references.pmid: 11246879
references.citation: J Biol Chem. 1993 Aug 5;268(22):16113-5
references.pmid: 8344895
references.citation: Diabetes. 1992 Apr;41(4):465-75
references.pmid: 1535055
references.citation: Diabetes. 2011 Jul;60(7):1832-7
references.pmid: 21709278
references.citation: Diabetes. 1990 Jul;39(7):865-70
references.pmid: 2354749
references.citation: J Clin Invest. 1998 Jun 1;101(11):2377-86
references.pmid: 9616209
references.citation: J Biol Chem. 1993 Sep 5;268(25):18442-5
references.pmid: 8360145