Resveratrol Increases Glucose Induced GLP-1 Secretion in Mice: A Mechanism which Contributes to the Glycemic Control

被引:133
|
作者
Dao, Thi-Mai Anh [1 ,2 ,3 ]
Waget, Aurelie [1 ,2 ]
Klopp, Pascale [1 ,2 ]
Serino, Matteo [1 ,2 ]
Vachoux, Christelle [1 ,2 ]
Pechere, Laurent [4 ]
Drucker, Daniel J. [5 ]
Champion, Serge [3 ]
Barthelemy, Sylvain [6 ]
Barra, Yves [3 ]
Burcelin, Remy [1 ,2 ]
Seree, Eric [3 ]
机构
[1] Fac Med Toulouse, INSERM, U1048, Inst Rech Malad Metab & Cardiovasc,I2MC, F-31073 Toulouse, France
[2] Univ Toulouse, UPS, Inst Malad Metab & Cardiovasc, Hop Rangueil, Toulouse, France
[3] Inst Natl Rech Agron 1260, Fac Pharm, Marseille, France
[4] ENTERONOVA SAS, Toulouse, France
[5] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Med, Toronto, ON M5G 1X5, Canada
[6] YVERY SARL, Marseille, France
来源
PLOS ONE | 2011年 / 6卷 / 06期
关键词
GLUCAGON-LIKE PEPTIDE-1; MITOCHONDRIAL-FUNCTION; INSULIN-SECRETION; SIRT1; OBESITY; INFLAMMATION; EXPRESSION; ACTIVATOR; DISEASE;
D O I
10.1371/journal.pone.0020700
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Resveratrol (RSV) is a potent anti-diabetic agent when used at high doses. However, the direct targets primarily responsible for the beneficial actions of RSV remain unclear. We used a formulation that increases oral bioavailability to assess the mechanisms involved in the glucoregulatory action of RSV in high-fat diet (HFD)-fed diabetic wild type mice. Administration of RSV for 5 weeks reduced the development of glucose intolerance, and increased portal vein concentrations of both Glucagon-like peptid-1 (GLP-1) and insulin, and intestinal content of active GLP-1. This was associated with increased levels of colonic proglucagon mRNA transcripts. RSV-mediated glucoregulation required a functional GLP-1 receptor (Glp1r) as neither glucose nor insulin levels were modulated in Glp1r-/- mice. Conversely, levels of active GLP-1 and control of glycemia were further improved when the Dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin was co-administered with RSV. In addition, RSV treatment modified gut microbiota and decreased the inflammatory status of mice. Our data suggest that RSV exerts its actions in part through modulation of the enteroendocrine axis in vivo.
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页数:9
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