Lipides, Nutrition, Cancer
Séminaires LNC
Année 2013

Intervenant : Dr Tony Jourdan
Institut : Laboratory of physiologic studies, Bethesda MD
Date : 17 septembre 2013 - 14h00
Lieu : Faculté de Médecine - Amphi Martin (1er étage)
Sujet : Endocannabinoid-activated Nlrp3 inflammasome in infiltrating macrophages mediates β-cell loss in type 2 diabetes.

Background: Type-2 diabetes (T2DM) progresses from compensated insulin resistance to β-cell failure resulting in uncompensated hyperglycemia, a process replicated in the Zucker diabetic fatty (ZDF) rat. The Nlrp3 inflammasome has been implicated in obesity-induced insulin resistance and β-cell failure. Endocannabinoids contribute to insulin resistance via activation of peripheral CB1 receptors (CB1R), and also promote β-cell failure.

Results & conclusions: Here we show that β-cell failure in adult ZDF rats is associated with CB1R-activation of the Nlrp3-ASC inflammasome in M1 macrophages infiltrating pancreatic islets, but not in β-cells. These effects are replicated in vitro by incubating human or rodent macrophages but not macrophages from CB1R-deficient (Cnr1­–/–)­­­ or Nlrp3–/– mice with the endocannabinoid anandamide. CB1R blockade, in vivo depletion of macrophages or macrophage-specific knockdown of CB1R reverses or prevents these changes, and restores normoglycemia and glucose-induced insulin secretion. These findings implicate macrophage-derived endocannabinoids in inflammasome activation and β-cell failure, and identify macrophage CB1R as therapeutic targets in T2DM.


Invitation: Bruno Verges UMR866

Le séminaire aura lieu à la Faculté de Médecine Dijon Amphi Martin à 14h00

Renseignements - Tel: 03 80 39 34 68.