title: Resveratrol increases glucose induced GLP-1 secretion in mice: a mechanism which contributes to the glycemic control.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1048, Institut de recherche sur les Maladies Métaboliques et Cardiovasculaire, I2MC, Toulouse, France.
authors.forename: Thi-Mai Anh
authors.initials: TM
authors.lastname: Dao
authors.forename: Aurélie
authors.initials: A
authors.lastname: Waget
authors.forename: Pascale
authors.initials: P
authors.lastname: Klopp
authors.forename: Matteo
authors.initials: M
authors.lastname: Serino
authors.forename: Christelle
authors.initials: C
authors.lastname: Vachoux
authors.forename: Laurent
authors.initials: L
authors.lastname: Pechere
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Drucker
authors.forename: Serge
authors.initials: S
authors.lastname: Champion
authors.forename: Sylvain
authors.initials: S
authors.lastname: Barthélemy
authors.forename: Yves
authors.initials: Y
authors.lastname: Barra
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Eric
authors.initials: E
authors.lastname: Sérée
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D018149:Glucose Intolerance / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000382:microbiology; D008297:Male; D054892:Metagenome / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018027:Receptors, Glucagon / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D013267:Stilbenes; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D000077185:Resveratrol