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Toxicol Lett. 2013 May 10;219(1):35-41. doi: 10.1016/j.toxlet.2013.02.013. Epub 2013 Feb 28.

Increased vulnerability to β-cell destruction and diabetes in mice lacking NAD(P)H:quinone oxidoreductase 1.

Author information

1
Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-806, Republic of Korea.

Abstract

NAD(P)H:quinone oxidoreductase 1 (NQO1) has been known to protect cells against stressors, including the diabetogenic reagent streptozotocin (STZ). The present study demonstrated that NQO1 deficiency resulted in increased pancreatic β-cell death induced by multiple low dose of STZ (MLDS) injections. NQO1 knockout (KO) mice showed hyperglycemia, body weight loss, impaired glucose clearance rate and a lower plasma insulin level after MLDS treatment. Moreover, β-cell mass and pancreatic insulin content were significantly lower in KO mice than in wild-type (WT) mice after MLDS treatment. Five days after the first STZ treatment, the islets of KO mice had substantially more TUNEL-positive β-cells than those of WT mice, but there was no difference in the regeneration of β-cells between KO mice and WT mice. At the same time, MLDS-treated KO mice showed significantly increased apoptotic markers in β-cells, including cleaved caspase 3, Smac/DIABLO and AIF (apoptosis inducing factor) in the cytoplasm. These results suggest that mice deficient in NQO1 are vulnerable to MLDS-induced β-cell destruction and diabetes, caused by increase of β-cell apoptosis in pancreas.

PMID:
23458895
DOI:
10.1016/j.toxlet.2013.02.013
[Indexed for MEDLINE]

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