Naringin Protects Pancreatic β-Cells Against Oxidative Stress-Induced Apoptosis by Inhibiting Both Intrinsic and Extrinsic Pathways in Insulin-Deficient Diabetic Mice

Abstract

Scope: Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear.

Methods and results: To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ). Naringin dose-dependently ameliorated hyperglycemia and islet dysfunction in insulin-deficient diabetic mice. Naringin counteracted STZ-induced β-cell apoptosis by inhibiting both the intrinsic (mitochondria-mediated) and extrinsic (death receptor-mediated) pathways. Furthermore, these protective effects were associated with suppression of DNA damage response and nuclear factor-kappa B- and mitogen-activated protein kinase-mediated signaling pathways, as well as reduction of reactive oxygen species accumulation and pro-inflammatory cytokine production in the pancreas.

Conclusion: Taken together, our study provides insights into the underlying mechanisms through which naringin protects the pancreatic β-cells against oxidative stress-induced apoptosis.

Keywords: apoptosis; diabetes; naringin; oxidative stress; pancreatic β-cells.