title: Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury.
abstract: Accumulating evidence shows that a gut-released hormone, the glucagon-like peptide-1 (GLP-1), has not only a glucose-lowering effect but also a renoprotective effect against kidney injury. In this study, we investigated whether a dipeptidyl peptidase (DPP) IV inhibitor has a protective effect against tacrolimus-induced renal injury. Rats were treated with tacrolimus (1.5 mg/kg, subcutaneously) and the DPP IV inhibitor MK0626 (10 or 20 mg/kg, oral gavage) for 4 weeks. MK0626 treatment attenuated tacrolimus-induced renal dysfunction, tubulointerstitial fibrosis, and arteriolopathy. Moreover, these improvements were accompanied by a reduction in oxidative stress and apoptosis. MK0626 treatment increased the blood level of GLP-1 and the level of its receptor in tissue sections but did not alter the levels of other DPP IV substrates, such as neuropeptide Y and the stromal cell-derived factor-1. These data suggest that DPP IV inhibition has an important role in the renoprotection against tacrolimus-induced nephrotoxicity via antioxidative and antiapoptotic effects and preservation of the GLP-1 system.
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul, Korea.|Transplant Research Center, Seoul, Korea.
authors.forename: Sun W
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul, Korea.|Transplant Research Center, Seoul, Korea.
authors.forename: Long
authors.initials: L
authors.lastname: Jin
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul, Korea.|Transplant Research Center, Seoul, Korea.
authors.forename: Shang G
authors.initials: SG
authors.lastname: Piao
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul, Korea.|Division of Nephrology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Byung H
authors.initials: BH
authors.lastname: Chung
authors.affiliation: Convergent Research Consortium for Immunologic Disease, Seoul, Korea.|Transplant Research Center, Seoul, Korea.|Division of Nephrology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chul W
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D065095:Calcineurin Inhibitors / Q000009:adverse effects* / Q000737:chemistry; D004039:Diet, Sodium-Restricted / Q000009:adverse effects; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016559:Tacrolimus / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D065095:Calcineurin Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007166:Immunosuppressive Agents; C570834:MK0626; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D016559:Tacrolimus; D000097789:Glucagon-Like Peptide-1 Receptor Agonists