| Title | Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity |
| Authors | Zhou Shutong Yu Dongni Ning Shangyong Zhang Heli Jiang Lei He Lei Li Miao Sun Mingxiao |
| Affiliation | Peking University Fifth School of Clinical Medicine, Beijing Hospital, Beijing, China. |
| Issue Date | 2015 |
| Publisher | cellular physiology and biochemistry international journal of experimental cellular physiology biochemistry and pharmacology |
| Citation | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology.2015,35,(6),2135-48. |
| Abstract | The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and β cell dysfunction in obesity.In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 β cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed.ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 β cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in β cells.Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with β cell dysfunction through ROS production. ? 2015 S. Karger AG, Basel. |
| URI | http://hdl.handle.net/20.500.11897/341297 |
| ISSN | 1421-9778 |
| DOI | 10.1159/000374019 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京医院 |
