Ye Jin Lim1, Jung Ho Kim1, Jeong Hoon Pan2, Jae Kyeom Kim2, Tae-Sik Park3, Young Jun Kim1, Jin Hyup Lee1,* and Jun Ho Kim1,*
1Department of Food and Biotechnology, Korea University, Sejong, South Korea
2School of Human Environmental Sciences, University of Arkansas, Fayetteville, Arkansas, USA
3Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Inchon, South Korea
*Correspondence: Jin Hyup Lee, Jun Ho Kim
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 (NF-κB)- and mitogen-activated protein kinase (MAPK)-mediated signaling pathways, as well as reduction of reactive oxygen species accumulation and proinflammatory 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