MST1 deletion protects β-cells in a mouse model of diabetes

The pro-apoptotic kinase Mammalian Sterile 20-like kinase 1 (MST1), an integral component of the Hippo pathway, is a key regulator of organ size, stress response, and tissue homeostasis; its aberrant hyperactivation is linked to multiple pathological disorders including diabetes. Here we show that MST1 deletion in mice resulted in improved glucose tolerance and insulin secretion, and restored pancreatic beta-cell mass as a result of improved beta-cell survival and proliferation in the combined high fat/high sucrose and streptozotocin (HFS/STZ) model of beta-cell destruction and diabetes. Importantly, the glucose-lowering effects in the MST1-knockout (KO) mice could be accounted to the enhanced beta-cell mass and improved insulin secretion without changes in insulin sensitivity. Metabolic and morphological data suggest that normalization of blood glucose and insulin secretion, islet architecture, and beta-cell mass by MST1 deletion in response to diabetes-induced injury occurs as a result of improved beta-cell survival and proliferation establishing MST1 as potent regulator of physiological beta-cell turnover.

Automated summary

MST1, an integral component of the Hippo pathway, plays a key role in regulating organ size, stress response, and tissue homeostasis. Its deletion can improve glucose tolerance and insulin secretion, restore pancreatic beta-cell mass, and enhance beta-cell survival and proliferation in response to diabetes-induced injury.