| Improved Insulin Sensitivity after Long-Term Treatment with AT1 Blockers Is Not Associated with PPARγ Target Gene Regulation. | |
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MedLine Citation:
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PMID: 22253423 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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In both cell culture experiments and in vivo studies, a number of angiotensin II type 1 (AT(1)) receptor antagonists activated the peroxisome proliferator-activated receptor-γ (PPARγ). This mechanism has been discussed to be, at least in part, responsible for the improvement in glucose metabolism observed in animal studies and clinical trials. To investigate whether the PPARγ-dependent mechanism may represent a valid target for chronic therapy, spontaneously hypertensive rats (SHR) were fed either with a cafeteria diet (CD) or standard chow. CD-fed SHR were simultaneously treated with either telmisartan (TEL; 8 mg/kg(body weight)·d) or candesartan (CAND; 10 mg/kg(body weight)·d) for 3 months because TEL, but not CAND, has been demonstrated to be a strong activator of PPARγ. After 3 months, chow- and CD-fed controls were hypertensive, whereas TEL and CAND treatment resulted in normalized blood pressures in SHR. Body weight and the amount of abdominal fat (determined by magnetic resonance imaging) were higher in CD- than in chow-fed SHR. After TEL or CAND, body weight, abdominal fat quantity, and adipocyte size returned to normal. In glucose tolerance tests, the glucose responses were comparable in the TEL- and CAND-treated SHR and obese controls, whereas the insulin response was almost halved by AT(1) blockade. Expression of PPARγ target genes aP2, FAT CD36, FASn, and PEPCK remained unaltered at the protein level in visceral fat after TEL and CAND compared with the CD-fed controls. Because the expression of examined PPARγ target genes was not affected, we concluded that improved insulin sensitivity after long-term treatment with AT(1) blockers was not related to a PPARγ-dependent mechanism. |
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Authors:
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Helge Müller-Fielitz; Julia Landolt; Marc Heidbreder; Stefan Werth; Florian M Vogt; Olaf Jöhren; Walter Raasch |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Experimental and Clinical Pharmacology and Toxicology (H.M.-F., J.L., M.H., S.W., O.J.,W.R.) and the Clinic for Radiology and Nuclear Medicine (F.M.V.), University of 23538 Lübeck, Germany. |
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