Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist

• Published in: Biochemical and biophysical research communications Vol. 332; no. 4; pp. 927 - 933
• Main Authors: Nakayama, Mieko, Inoguchi, Toyoshi, Sonta, Toshiyo, Maeda, Yasutaka, Sasaki, Shuji, Sawada, Fumi, Tsubouchi, Hirotaka, Sonoda, Noriyuki, Kobayashi, Kunihisa, Sumimoto, Hideki, Nawata, Hajime
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2005
• Subjects: Administration, Oral; Aldehydes - pharmacology; Angiotensin II; Angiotensin II - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensins - metabolism; Animals; Body Weight; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - pharmacology; Diabetes Mellitus, Type 2 - metabolism; Disease Models, Animal; Insulin - metabolism; Islets of Langerhans - enzymology; Islets of Langerhans - metabolism; Membrane Glycoproteins - metabolism; Membrane Transport Proteins - metabolism; Mice; Mice, Inbred C57BL; NAD(P)H oxidase; NADPH Oxidase 2; NADPH Oxidases - biosynthesis; NADPH Oxidases - metabolism; Oxidative Stress; Phosphoproteins - metabolism; Rats; Rats, Inbred OLETF; Rats, Long-Evans; Tetrazoles - pharmacology; Time Factors; Type 2 diabetes; Valine - analogs & derivatives; Valine - pharmacology; Valsartan; β-cell; Type 2 diabetes; Oxidative stress; β-cell; Angiotensin II; NAD(P)H oxidase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.05.065

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 β-cell damage.