| CCR2 antagonism improves insulin resistance, lipid metabolism, and diabetic nephropathy in type 2 diabetic mice. | |
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MedLine Citation:
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PMID: 20686445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chemokine ligand 2 (CCL2) binds to its receptor C-C chemokine receptor 2 (CCR2), initiating tissue inflammation, and recent studies have suggested a beneficial effect of a blockade of this pathway in diabetic nephropathy. To investigate the mechanism of protection, we studied the effect of RS504393, a CCR2 antagonist, on insulin resistance and diabetic nephropathy in db/db mice. Administering this antagonist improved insulin resistance as confirmed by various biomarkers, including homeostasis model assessment index levels, plasma insulin levels, and lipid abnormalities. Mice treated with the antagonist had a significant decrease in epididymal fat mass as well as phenotypic changes of adipocytes into small differentiated forms with decreased CCL2 expression and lipid hydroperoxide levels. In addition, treatment with the CCR2 antagonist markedly decreased urinary albumin excretion, mesangial expansion, and suppressed profibrotic and proinflammatory cytokine synthesis. Furthermore, the CCR2 antagonist improved lipid metabolism, lipid hydroperoxide, cholesterol, and triglyceride contents of the kidney, and decreased urinary 8-isoprostane levels. Hence, our findings suggest that CCR2 antagonists can improve insulin resistance by modulation of the adipose tissue and restore renal function through both metabolic and anti-fibrotic effects in type 2 diabetic mice. |
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Authors:
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Young Sun Kang; Mi Hwa Lee; Hye Kyoung Song; Gang Jee Ko; Oh Sung Kwon; Tae Kyung Lim; Sung Hwan Kim; Sang Youb Han; Kum Hyun Han; Ji Eun Lee; Jee Young Han; Hyoung Kyu Kim; Dae Ryong Cha |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-04 |
Journal Detail:
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Title: Kidney international Volume: 78 ISSN: 1523-1755 ISO Abbreviation: Kidney Int. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-15 Completed Date: 2011-02-09 Revised Date: 2012-04-09 |
Medline Journal Info:
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Nlm Unique ID: 0323470 Medline TA: Kidney Int Country: United States |
Other Details:
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Languages: eng Pagination: 883-94 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Department of Internal Medicine, Korea University, Ansan City, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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drug effects,
metabolism Adiponectin / blood Adipose Tissue / drug effects*, metabolism, pathology Albuminuria / drug therapy, metabolism Animals Anti-Inflammatory Agents / pharmacology* Biological Markers / blood Blood Glucose / metabolism Cells, Cultured Cytokines / genetics, metabolism Diabetes Mellitus, Type 2 / complications, drug therapy*, metabolism, physiopathology Diabetic Nephropathies / drug therapy*, etiology, metabolism, physiopathology Disease Models, Animal Fibrosis Gene Expression Regulation Hemoglobin A, Glycosylated / metabolism Hypoglycemic Agents / pharmacology* Inflammation Mediators / metabolism Insulin / blood Insulin Resistance* Kidney / drug effects*, metabolism, pathology Lipid Metabolism / drug effects* Lipid Peroxidation / drug effects Male Mice Mice, Inbred C57BL Receptors, CCR2 / antagonists & inhibitors*, metabolism Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Adipoq protein, mouse; 0/Anti-Inflammatory Agents; 0/Biological Markers; 0/Blood Glucose; 0/Ccr2 protein, mouse; 0/Cytokines; 0/Hemoglobin A, Glycosylated; 0/Hypoglycemic Agents; 0/Inflammation Mediators; 0/Insulin; 0/Receptors, CCR2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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