Increased levels of plasma cholesterol are a common feature of patient of type 2 diabetes. However, the links between elevated levels of low-density lipoprotein (LDL) and dysfunction of β-cells are still unclear. Methods:
mice were fed with a high-fat, cholesterol-rich diet for 8 weeks. Blood samples were collected from the mice for measurement of plasma glucose, lipids. The pancreas were embedded in OCT compound and frozen immediately in liquid nitrogen for further analysis. To examine the effects of LDL on β-cell function, insulin content, cell apoptosis and ROS production were measured in pancreatic islets of apoE-/-
mice and mouse pancreatic β–cell line NIT-1. Relative cell signal pathways were determined by Western blot. Results:
Decreased insulin content and increased apoptosis and ROS production were found in pancreatic islets of apoE-/-
mice, accompanied by elevated plasma LDL. The ROS levels were significantly enhanced in NIT-1 cells exposed to LDL. Reduced insulin synthesis and glucose-stimulated insulin secretion and elevated apoptosis were reversed by suppression of NOX2 expression. Moreover, LDL induced dysfunction and apoptosis of pancreatic NIT-1 cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. Conclusions:
NOX2-derived ROS may play a key role in LDL-induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways.
Shu Wang and Jian Li, Beijing Institute of Geriatrics, Beijing Hospital, Ministry of Health No.1, Dahua Road, Dong Dan, Beijing 100730 (China) Tel.+8610-58115048(o), Fax +86 10 65237929 E-Mail firstname.lastname@example.org (J. Li), email@example.com (S.Wang)
Accepted: June 15, 2012
Published online: July 06, 2012
Number of Print Pages : 11
Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry and Pharmacology)
Vol. 30, No. 2, Year 2012 (Cover Date: July 2012)
Journal Editor: Guggino W. (Baltimore, Md.), Lang F. (Tübingen)
ISSN: 1015-8987 (Print), eISSN: 1421-9778 (Online)
For additional information: http://www.karger.com/CPB
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