title: MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells.
abstract: BACKGROUND
  Increasing evidence suggests that miR-126 participates in the glucose homeostasis through its target molecules. Although bioinformatics analysis predicts that miR-126 can bind with the insulin receptor substrate-2(IRS-2) mRNA at the "seed sequence", but there are still no definitely reports to support it. In this study, we provided evidences that IRS-2 was one of the target genes of miR-126. And miR-126 has a proliferation inhibiting effects in INS-1 β cells, mainly through the suppression of IRS-2.
  
  
  METHODS
  The 3'-UTR of IRS-2 regulated by miR-126 was analyzed by the luciferase assay and western blot. Furthermore, proliferation of INS-1 β cells stimulated by glucose was tested, and the association between IRS-2 and miR-126 were analyzed.
  
  
  RESULTS
  We found that mutation of only three of the 6 "seed sequences" can eliminate the inhibition effect of miR-126. In INS-1 β cells, administration of miR-126 suppresses the proliferation, together with the unbalanced down-regulation of IRS-2 and IRS-1. Over-expression of IRS-2 can reverse the proliferation effect of miR-126, while not of IRS-1. These results suggested that miR-126 inhibited the β-cell proliferation via the inhibition of IRS-2 instead of IRS-1.Additionally, we also found that high glucose and insulin could stimulate the rapid production of endogenous miR-126 within 6 hours, together with the short term suppression of IRS-1 and IRS-2 expression, and intensify the unbalanced expression of IRS-1 and IRS-2.
  
  
  CONCLUSIONS
  IRS-2 was one of the targets of miR-126. MiR-126 inhibited the β-cell proliferation through IRS-2 instead of IRS-1. MiR-126 may take part in the glucose homeostasis both through its target IRS-2 and IRS-1. The unbalance between IRS-1 and IRS-2 caused by miR-126 may play an important role in type 2 diabetes.
authors.affiliation: The Department of Physiology, Ningxia Medical University, Yinchuan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Tao
authors.affiliation: The Department of Physiology, Ningxia Medical University, Yinchuan, China.|Jiamusi Central Hospital, Department of Epilepsy, Jiamusi, Hei Long Jiang, China.
authors.forename: Meng-meng
authors.initials: MM
authors.lastname: Wang
authors.affiliation: The Department of Physiology, Ningxia Medical University, Yinchuan, China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Ningxia Key Lab of Cerebrocranial Diseases, the National Key Laboratory Incubation Base, Yinchuan, China.
authors.forename: Shao-ping
authors.initials: SP
authors.lastname: Zhang
authors.affiliation: General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Chun-hui
authors.initials: CH
authors.lastname: Wang
authors.affiliation: The Department of Physiology, Ningxia Medical University, Yinchuan, China.|The Department of Physiology, Second Military Medical University, Shanghai, China.
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Yuan
authors.affiliation: Ningxia Key Lab of Cerebrocranial Diseases, the National Key Laboratory Incubation Base, Yinchuan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Lan-jie
authors.initials: LJ
authors.lastname: He
authors.affiliation: The Department of Physiology, Ningxia Medical University, Yinchuan, China.|Ningxia Key Lab of Cerebrocranial Diseases, the National Key Laboratory Incubation Base, Yinchuan, China.
authors.forename: Qi-kuan
authors.initials: QK
authors.lastname: Hu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000494:pharmacology*; D051381:Rats
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C571458:MIRN126 microRNA, rat; D035683:MicroRNAs; D005947:Glucose