Developmental Role of Macrophage Cannabinoid-1 Receptor Signaling in Type 2 Diabetes.

ABSTRACT: Islet inflammation promotes β-cell loss and type 2 diabetes (T2D), a process replicated in Zucker Diabetic Fatty (ZDF) rats in which β-cell loss has been linked to cannabinoid-1 receptor (CB₁R)-induced proinflammatory signaling in macrophages infiltrating pancreatic islets. Here, we analyzed CB₁R signaling in macrophages and its developmental role in T2D. ZDF rats with global deletion of CB₁R are protected from β-cell loss, hyperglycemia, and nephropathy that are present in ZDF littermates. Adoptive transfer of CB₁R^-/- bone marrow to ZDF rats also prevents β-cell loss and hyperglycemia but not nephropathy. ZDF islets contain elevated levels of CB₁R, interleukin-1β, tumor necrosis factor-α, the chemokine CCL2, and interferon

SUBMITTER: Jourdan T 

PROVIDER: S-EPMC5360301 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature