| Sitagliptin Promotes Macrophage-to-feces Reverse Cholesterol Transport Through Reduced Intestinal Cholesterol Absorption in Obese Insulin Resistant CETP-apoB100 Transgenic Mice. | |
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MedLine Citation:
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PMID: 22268579 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in type 2 diabetes, but their benefits on reverse cholesterol transport (RCT) remain unknown. We evaluated the effects of DPP-4 inhibitor sitagliptin 500mg/kg/day on RCT in obese insulin resistant CETP-apoB100 transgenic mice. Metformin 300mg/kg/day orally was used as a reference compound. Both metformin and sitagliptin showed the expected effects on glucose parameters. Although no significant effect was observed on total cholesterol and HDL-c levels, sitagliptin, but not metformin, increased fecal cholesterol mass excretion by 132% (p<0.001 vs. vehicle), suggesting a potent effect on cholesterol metabolism. Mice were then injected i.p. with (3) H-cholesterol labelled macrophages to measure RCT over 48 hours. Compared to vehicle, sitagliptin significantly increased macrophage-derived (3) H-cholesterol fecal excretion by 39%. Administration of (14) C-cholesterol labelled olive oil orally showed a significant reduction of (14) C-tracer plasma appearance over time with sitagliptin, indicating that this drug promotes RCT through reduced intestinal cholesterol absorption. |
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Authors:
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François Briand; Quentin Thieblemont; Rémy Burcelin; Thierry Sulpice |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-23 |
Journal Detail:
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Title: Diabetes, obesity & metabolism Volume: - ISSN: 1463-1326 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883645 Medline TA: Diabetes Obes Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 Blackwell Publishing Ltd. |
Affiliation:
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Physiogenex SAS, Prologue Biotech, Rue Pierre et Marie Curie, B.P. 28262, 31682 Labège-Innopole, France. INSERM U1048, I2MC, 1 avenue Jean Poulhès, B.P. 84225, 31400 Toulouse, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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