| Dipeptidyl Peptidase (DPP) IV Inhibitor Attenuates Kidney Injury in Streptozotocin Induced Diabetic Rats. | |
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MedLine Citation:
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PMID: 22025647 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Dipeptidyl peptidase (DPP) IV inhibitors are likely beneficial for treating diabetic complication and modulating glucagon-like peptide-1 receptor (GLP-1R) expression. The aim of this study was to determine if the DPP IV inhibitor, LAF237, has renoprotective qualities in streptozotocin-induced diabetic rats. Diabetic and non-diabetic rats were treated with an oral dose of 4 or 8mg/kg/day LAF237 or placebo for 24 weeks, and renal injury was observed by light and electron microscopy. We also assessed DPP IV activity, GLP-1 level, cAMP and 8-OhdG excretion, and GLP-1R, caspase 3 and transforming growth factor (TGF)-β1 expression. LAF237 significantly decreased proteinuria, albuminuria and urinary albumin/creatinine ratio, improved creatinine clearance, and dose-dependently inhibited interstitial expansion, glomerulosclerosis and the thickening of the glomerular basement membrane in diabetic rats. Notably, LAF237 markedly down-regulated DPP IV activity and increased GLP-1 levels, which likely prevented oxidative DNA damage and renal cell apoptosis by activating the GLP-1R and modulating cAMP. Renoprotection was also associated with a reduction in TGF-β1 overexpression. Our study suggests that DPP IV inhibitors may ameliorate diabetic nephropathy as well as reduce the overproduction of TGF-β1. The observed renoprotection is probably attributable to inhibition of DPP IV activity, mimicking incretin action and activating the GLP-1R. |
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Authors:
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Wei Jing Liu; Shu Hua Xie; Yu Nin Liu; Won Kim; Heung Yong Jin; Sung Kwang Park; Yi Ming Shao; Tae Sun Park |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-24 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: - ISSN: 1521-0103 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Nephrology; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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