Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Nov;370(1-2):103-13.
doi: 10.1007/s11010-012-1402-z. Epub 2012 Aug 22.

NADPH oxidase 2 plays a critical role in dysfunction and apoptosis of pancreatic β-cells induced by very low-density lipoprotein

Juan Jiao  1 , Lin Dou, Miao Li, Yonggang Lu, Han-Bang Guo, Yong Man, Shu Wang, Jian Li
Affiliations

NADPH oxidase 2 plays a critical role in dysfunction and apoptosis of pancreatic β-cells induced by very low-density lipoprotein

Juan Jiao et al. Mol Cell Biochem. 2012 Nov.

Abstract

In type 2 diabetes, pancreatic β-cells cannot secret enough insulin compensate for insulin resistance, which are often accompanied by abnormality in lipid metabolism such as hypertriglyceridemia. It is reported that oxidative stress is involved in pancreatic β-cell dysfunction. However, molecular mechanisms linking between excessive generations of reactive oxygen species (ROS) and β-cell dysfunction and apoptosis induced by high levels of very low-density lipoprotein (VLDL) are poorly understood. In this study, we test the hypothesis that NADPH oxidase 2 (NOX2)-derived ROS may play a key role in dysfunction and apoptosis of pancreatic β-cell induced by VLDL. Our results show that the ApoCIII transgenic mice displayed increased serum TG levels, enhanced generation of ROS and impaired insulin content in pancreatic β-cells. In vitro, the treatment of pancreatic NIT-1 cells with 1 mg/ml VLDL for 12 h stimulated NOX2-derived ROS generation, decreased expression and secretion of insulin. Furthermore, we found that VLDL induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. In conclusion, our data demonstrate a critical role of NOX2-derived ROS in dysfunction and apoptosis through JNK and p53 pathways in pancreatic β-cells induced by VLDL.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15554-9 - PubMed
    1. Nature. 2000 Apr 13;404(6779):787-90 - PubMed
    1. Nature. 2001 Dec 13;414(6865):788-91 - PubMed
    1. Endocrinology. 2002 Sep;143(9):3449-53 - PubMed
    1. Am J Pathol. 2000 Jan;156(1):237-44 - PubMed

Publication types

MeSH terms

LinkOut - more resources