| Bezafibrate regulates the expression and enzyme activity of 11beta-hydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes. | |
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MedLine Citation:
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PMID: 17190905 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A clinically employed antihyperlipidemic drug, bezafibrate, has been characterized as a PPAR(alpha, -gamma, and -delta) pan-agonist in vitro. Recent extended trials have highlighted its antidiabetic properties in humans. However, the underlying molecular mechanism is not fully elucidated. The present study was designed to explore potential regulatory mechanisms of intracellular glucocorticoid reactivating enzyme, 11beta-HSD1 and anti-diabetic hormone, adiponectin by bezafibrate in murine adipose tissue, and cultured adipocytes. Treatment of db/db mice with bezafibrate significantly ameliorated hyperglycemia and insulin resistance, accompanied by a marked reduction of triglyceride and nonesterified fatty acids. Despite equipotent in lipid-lowering effects, another fibrate, fenofibrate, did not show such beneficial effects on glycemic control. Treatment of bezafibrate caused a marked decrease in the mRNA level of 11beta-HSD1 preferentially in adipose tissue of db/db mice (-47%, P<0.05), concomitant with a significant increase in plasma adiponectin level (+37%, P<0.01). Notably, treatment of bezafibrate caused a marked decrease in the mRNA level (-34%, P<0.01) and enzyme activity (-32%, P<0.01) of 11beta-HSD1, whereas the treatment substantially augmented the expression (+71%, P<0.01) and secretion (+27%, P<0.01) of adiponectin in 3T3-L1 adipocytes. Knockdown of 11beta-HSD1 by siRNA confirmed that 11beta-HSD1 acts as a distinct oxoreductase in adipocytes and validated the enzyme activity assays in the present study. Effects of bezafibrate on regulation of 11beta-HSD1 and adiponectin in murine adipocytes were comparable with those in thiazolidinediones. This is the first demonstration that bezafibrate directly regulates 11beta-HSD1 and adiponectin in murine adipocytes, both of which may contribute to metabolically-beneficial effects by bezafibrate. |
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Authors:
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Shigeru Nakano; Yoichi Inada; Hiroaki Masuzaki; Tomohiro Tanaka; Shintaro Yasue; Takako Ishii; Naoki Arai; Ken Ebihara; Kiminori Hosoda; Kazuyasu Maruyama; Yoshinobu Yamazaki; Nobuo Shibata; Kazuwa Nakao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-26 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: 292 ISSN: 0193-1849 ISO Abbreviation: Am. J. Physiol. Endocrinol. Metab. Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-04-02 Completed Date: 2007-05-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: E1213-22 Citation Subset: IM |
Affiliation:
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Pharmacology Research Laboratory R and D, Kissei Pharmaceutica, Nagano, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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11-beta-Hydroxysteroid Dehydrogenase Type 1
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antagonists & inhibitors,
genetics,
metabolism* 3T3-L1 Cells Adipocytes / drug effects, enzymology, metabolism* Adiponectin / blood, metabolism* Adipose Tissue / drug effects, enzymology, metabolism* Animals Antilipemic Agents / pharmacology* Bezafibrate / pharmacology* Diabetes Complications / physiopathology Diabetes Mellitus / genetics, metabolism*, pathology, physiopathology Fatty Acids, Nonesterified / blood Hyperglycemia / etiology, physiopathology Insulin Resistance Liver / pathology Male Mice Mice, Inbred Strains Organ Size / drug effects Oxidoreductases / metabolism Peroxisome Proliferator-Activated Receptors / agonists RNA, Messenger / antagonists & inhibitors RNA, Small Interfering / pharmacology Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Antilipemic Agents; 0/Fatty Acids, Nonesterified; 0/Peroxisome Proliferator-Activated Receptors; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Triglycerides; 41859-67-0/Bezafibrate; EC 1.-/Oxidoreductases; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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