Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury
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 agains...
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| Veröffentlicht in: | Laboratory investigation 2015-10, Vol.95 (10), p.1174-1185 |
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| creator | Lim, Sun W Jin, Long Piao, Shang G Chung, Byung H Yang, Chul W |
| description | 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. |
| doi_str_mv | 10.1038/labinvest.2015.93 |
| format | Article |
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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.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.2015.93</identifier><identifier>PMID: 26237274</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject><![CDATA[13/51 ; 692/308/1426 ; Animals ; Antioxidants - administration & dosage ; Antioxidants - therapeutic use ; Apoptosis - drug effects ; Biomarkers - blood ; Biomarkers - metabolism ; Calcineurin Inhibitors - adverse effects ; Calcineurin Inhibitors - chemistry ; Diet, Sodium-Restricted - adverse effects ; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; Dose-Response Relationship, Drug ; Fibrosis ; Glucagon-Like Peptide 1 - agonists ; Glucagon-Like Peptide 1 - antagonists & inhibitors ; Glucagon-Like Peptide 1 - blood ; Glucagon-Like Peptide-1 Receptor - agonists ; Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors ; Glucagon-Like Peptide-1 Receptor - metabolism ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - antagonists & inhibitors ; Kidney - blood supply ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Laboratory Medicine ; Male ; Medicine ; Medicine & Public Health ; Oxidative Stress - drug effects ; Pathology ; Random Allocation ; Rats, Sprague-Dawley ; Renal Insufficiency, Chronic - chemically induced ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - physiopathology ; Renal Insufficiency, Chronic - prevention & control ; research-article ; Tacrolimus - adverse effects ; Tacrolimus - antagonists & inhibitors ; Triazoles - administration & dosage ; Triazoles - therapeutic use]]></subject><ispartof>Laboratory investigation, 2015-10, Vol.95 (10), p.1174-1185</ispartof><rights>2015 United States & Canadian Academy of Pathology</rights><rights>United States & Canadian Academy of Pathology 2015</rights><rights>Copyright Nature Publishing Group Oct 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-a511cd8b638a482b2545b09b1505b4efe4f4e88143e05f378bd192e3f4ebea3e3</citedby><cites>FETCH-LOGICAL-c467t-a511cd8b638a482b2545b09b1505b4efe4f4e88143e05f378bd192e3f4ebea3e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26237274$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Sun W</creatorcontrib><creatorcontrib>Jin, Long</creatorcontrib><creatorcontrib>Piao, Shang G</creatorcontrib><creatorcontrib>Chung, Byung H</creatorcontrib><creatorcontrib>Yang, Chul W</creatorcontrib><title>Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>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.</description><subject>13/51</subject><subject>692/308/1426</subject><subject>Animals</subject><subject>Antioxidants - administration & dosage</subject><subject>Antioxidants - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - metabolism</subject><subject>Calcineurin Inhibitors - adverse effects</subject><subject>Calcineurin Inhibitors - chemistry</subject><subject>Diet, Sodium-Restricted - adverse effects</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - administration & dosage</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fibrosis</subject><subject>Glucagon-Like Peptide 1 - 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Sun W</au><au>Jin, Long</au><au>Piao, Shang G</au><au>Chung, Byung H</au><au>Yang, Chul W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>95</volume><issue>10</issue><spage>1174</spage><epage>1185</epage><pages>1174-1185</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><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.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>26237274</pmid><doi>10.1038/labinvest.2015.93</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/51 692/308/1426 Animals Antioxidants - administration & dosage Antioxidants - therapeutic use Apoptosis - drug effects Biomarkers - blood Biomarkers - metabolism Calcineurin Inhibitors - adverse effects Calcineurin Inhibitors - chemistry Diet, Sodium-Restricted - adverse effects Dipeptidyl-Peptidase IV Inhibitors - administration & dosage Dipeptidyl-Peptidase IV Inhibitors - therapeutic use Dose-Response Relationship, Drug Fibrosis Glucagon-Like Peptide 1 - agonists Glucagon-Like Peptide 1 - antagonists & inhibitors Glucagon-Like Peptide 1 - blood Glucagon-Like Peptide-1 Receptor - agonists Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors Glucagon-Like Peptide-1 Receptor - metabolism Immunosuppressive Agents - adverse effects Immunosuppressive Agents - antagonists & inhibitors Kidney - blood supply Kidney - drug effects Kidney - metabolism Kidney - pathology Laboratory Medicine Male Medicine Medicine & Public Health Oxidative Stress - drug effects Pathology Random Allocation Rats, Sprague-Dawley Renal Insufficiency, Chronic - chemically induced Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - physiopathology Renal Insufficiency, Chronic - prevention & control research-article Tacrolimus - adverse effects Tacrolimus - antagonists & inhibitors Triazoles - administration & dosage Triazoles - therapeutic use |
| title | Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury |
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