Lipides, Nutrition, Cancer
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
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