title: Curcumin protects against fructose-induced podocyte insulin signaling impairment through upregulation of miR-206.
abstract: METHODS
  Fructose consumption can induce insulin resistance and metabolic syndrome, which are associated with glomerular podocyte dysfunction and proteinuria. This study investigated whether fructose caused insulin signaling impairment in podocyte dysfunction and injury, and whether curcumin reduced these disturbances.
  
  
  RESULTS
  Rats were fed with 10% fructose for 6 weeks and then orally cotreated with curcumin for next 6 weeks. Metabolic syndrome, podocyte injury, microRNA expression, and insulin signaling were evaluated. Curcumin significantly alleviated fructose-induced podocyte injury and proteinuria, miR-206 low-expression, protein tyrosine phosphatase 1B (PTP1B) overexpression, as well as downregulation of insulin receptor, insulin receptor substrate 1, caveolin-1, protein kinase B, and extracellular signal-regulated kinases 1 and 2 phosphorylation in kidney cortex or glomeruli of fructose-fed rats. These effects were further confirmed in cultured differentiated podocytes exposed to 5 mM fructose in the presence or absence of curcumin, PTP1B siRNA, lentivirus-mediated PTP1B recombinant overexpression, miR-206 mimic, or miR-206 inhibitor transfection, showing that miR-206 upregulation may contribute to improve insulin signaling through regulating PTP1B expression.
  
  
  CONCLUSIONS
  Curcumin is suggested to activate miR-206 expression to downregulate PTP1B, and then improve insulin signaling, protect against fructose-induced glomerular podocyte injury, and proteinuria, which may provide new evidence regarding curcumin's effects on fructose-associated podocyte injury.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Song
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Qiao-Chu
authors.initials: QC
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D005632:Fructose / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000188:drug therapy; D035683:MicroRNAs / Q000235:genetics*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007328:Insulin; D035683:MicroRNAs; D020011:Protective Agents; C522220:mirn206 microRNA, rat; D005632:Fructose; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D003474:Curcumin
keywords: Curcumin; Fructose intake; Insulin resistance; Podocyte injury; miRNA-206