title: Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase.
abstract: The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy.
authors.affiliation: Division of Basic Medical Science, Hungkuang University , No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung City 43302, Taiwan.
authors.forename: Chiung-Huei
authors.initials: CH
authors.lastname: Peng
authors.forename: Yi-Sun
authors.initials: YS
authors.lastname: Yang
authors.forename: Kuei-Chuan
authors.initials: KC
authors.lastname: Chan
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
authors.forename: Mu-Lin
authors.initials: ML
authors.lastname: Chen
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D031584:Hibiscus / Q000737:chemistry*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000069476:Linagliptin; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D014746:Vimentin / Q000378:metabolism
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D059808:Polyphenols; D011687:Purines; D011799:Quinazolines; D014746:Vimentin; D000069476:Linagliptin; D018819:Dipeptidyl Peptidase 4; D005947:Glucose
keywords: diabetic nephropathy; epithelial to mesenchymal transition; insulin resistance; polyphenol extracts of Hibiscus sabdariffa; type 4 dipeptidyl peptidase