Lentinan Protects Against Pancreatic Beta-Cell Failure In Chronic Ethanol Consumption-Induced Diabetic Mice Via Enhancing Beta-Cell Antioxidant Capacity

Chronic ethanol consumption is a well-established independent risk factor for type 2 diabetes mellitus (T2DM). Recently, increasing studies have confirmed that excessive heavy ethanol exerts direct harmful effect on pancreatic beta-cell mass and function, which may be a mechanism of pancreatic beta-cell failure in T2DM. In this study, we evaluated the effect of Lentinan (LNT), an active ingredient purified from the bodies of Lentinus edodes, on pancreatic beta-cell apoptosis and dysfunction caused by ethanol and the possible mechanisms implicated. Functional studies reveal that LNT attenuates chronic ethanol consumption-induced impaired glucose metabolism in vivo. In addition, LNT ameliorates chronic ethanol consumption-induced beta-cell dysfunction, which is characterized by reduced insulin synthesis, defected insulin secretion and increased cell apoptosis. Furthermore, mechanistic assays suggest that LNT enhances beta-cell antioxidant capacity and ameliorates ethanol-induced oxidative stress by activating Nrf-2 antioxidant pathway. Our results demonstrated that LNT prevents ethanol-induced pancreatic beta-cell dysfunction and apoptosis, and therefore may be a potential pharmacological agent for preventing pancreatic beta-cell failure associated with T2DM and stress-induced diabetes.