Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist.
This study was undertaken to reveal the role of NAD(P)H oxidase in increased oxidative stress in islets of Type 2 diabetes. Immunostaining analysis showed that staining intensities of NAD(P)H oxidase components, gp91phox and p22phox, significantly increased in islets of animal models of Type 2 diabetes, OLETF rats (60 weeks of age) and db/db mice (14 weeks of age), compared with age-matched controls, respectively, correlating with increased levels of oxidative stress marker, 8-hydroxy-deoxyguanosine or 4-hydroxy-2-nonenal modified protein. In db/db mice, oral administration of angiotensin II Type 1 receptor antagonist valsartan (5 mg/kg) for 4 weeks significantly attenuated the increased expression of gp91phox and p22phox together with inhibition of oxidative stress and partially restored decreased insulin contents in islets. Angiotensin II-related increased expression of NAD(P)H oxidase may play an important role in increased oxidative stress in islets of Type 2 diabetes. This mechanism may be a novel therapeutic target for preventing beta-cell damage.
Nakayama
Mieko
M
Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Inoguchi
Toyoshi
T
Sonta
Toshiyo
T
Maeda
Yasutaka
Y
Sasaki
Shuji
S
Sawada
Fumi
F
Tsubouchi
Hirotaka
H
Sonoda
Noriyuki
N
Kobayashi
Kunihisa
K
Sumimoto
Hideki
H
Nawata
Hajime
H
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000447:Aldehydes / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000447:Aldehydes; D047228:Angiotensin II Type 1 Receptor Blockers; D000809:Angiotensins; D007328:Insulin; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D000080242:8-Hydroxy-2'-Deoxyguanosine; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; D003849:Deoxyguanosine; D014633:Valine; C027576:4-hydroxy-2-nonenal