Kindlin-2 protects pancreatic β cells through inhibiting NLRP3 inflammasome activation in diabetic mice.

Diabetes mellitus has been a major public health problem worldwide, characterized by insulin resistance and dysfunction of β-cells. A previous study showed that Kindlin-2 loss in β-cells dramatically reduces insulin secretion and decreases β-cell mass, resulting in severe diabetes-like phenotypes. It suggests that Kindlin-2 in β-cells play an important role in regulating glucose homeostasis. However, the effect of Kindlin-2 on the function of β-cells under chronic hyperglycemia in diabetes has not been explored. Here we report that Kindlin-2 overexpression ameliorates diabetes and improves insulin secretion in mice induced by streptozocin. In contrast, Kindlin-2 insufficiency exacerbates diabetes and promotes β-cells dysfunction and inflammation in β-cells induced by a high-fat diet (HFD). In vitro, Kindlin-2 overexpression prevented high-glucose (HG)-induced dysfunction in β-cells. Kindlin-2 overexpression also decreased the expression of pro-inflammatory cytokines and NLRP3 inflammasome expression in β-cells exposed to HG. Furthermore, the loss of Kindlin-2 aggravates the expression of inflammatory cytokines and NLRP3 induced by HG in β-cells. Collectively, we demonstrate that Kindlin-2 protects against diabetes by inhibiting NLRP3 inflammasome activation.