Siglec-7 Restores Beta-Cell Function And Survival And Reduces Inflammation In Pancreatic Islets From Patients With Diabetes

Chronic inflammation plays a key role in both type 1 and type 2 diabetes. Cytokine and chemokine production within the islets in a diabetic milieu results in beta-cell failure and diabetes progression. Identification of targets, which both prevent macrophage activation and infiltration into islets and restore beta-cell functionality is essential for effective diabetes therapy. We report that certain Sialic-acidbinding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on beta-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. Over-expression of Siglec-7 in diabetic islets reduced cytokines, prevented beta-cell dysfunction and apoptosis and reduced recruiting of migrating monocytes. Our data suggest that restoration of human Siglec-7 expression may be a novel therapeutic strategy targeted to both inhibition of immune activation and preservation of beta-cell function and survival.