title: Increased vulnerability to β-cell destruction and diabetes in mice lacking NAD(P)H:quinone oxidoreductase 1.
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.
authors: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-806, Republic of Korea.
authors: Seung-Hoon
authors: SH
authors: Yeo
authors: Jung-Ran
authors: JR
authors: Noh
authors: Yong-Hoon
authors: YH
authors: Kim
authors: Gil-Tae
authors: GT
authors: Gang
authors: Sang-Woo
authors: SW
authors: Kim
authors: Kyoung-Shim
authors: KS
authors: Kim
authors: Jung Hwan
authors: JH
authors: Hwang
authors: Minho
authors: M
authors: Shong
authors: Chul-Ho
authors: CH
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency* / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D013311:Streptozocin; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse