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

Mieko Nakayama; Toyoshi Inoguchi; Toshiyo Sonta; Yasutaka Maeda; Shuji Sasaki; Fumi Sawada; Hirotaka Tsubouchi; Noriyuki Sonoda; Kunihisa Kobayashi; Hideki Sumimoto; Hajime Nawata

doi:10.1016/j.bbrc.2005.05.065

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

Biochem Biophys Res Commun. 2005 Jul 15;332(4):927-33. doi: 10.1016/j.bbrc.2005.05.065.

Authors

Mieko Nakayama¹, Toyoshi Inoguchi, Toshiyo Sonta, Yasutaka Maeda, Shuji Sasaki, Fumi Sawada, Hirotaka Tsubouchi, Noriyuki Sonoda, Kunihisa Kobayashi, Hideki Sumimoto, Hajime Nawata

Affiliation

¹ Department of Medicine and Bioregulatory Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

PMID: 15922295
DOI: 10.1016/j.bbrc.2005.05.065

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

8-Hydroxy-2'-Deoxyguanosine
Administration, Oral
Aldehydes / pharmacology
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
NADPH Oxidase 2
NADPH Oxidases / biosynthesis*
NADPH Oxidases / metabolism
Oxidative Stress
Phosphoproteins / metabolism
Rats
Rats, Inbred OLETF
Rats, Long-Evans
Tetrazoles / pharmacology
Time Factors
Valine / analogs & derivatives*
Valine / pharmacology
Valsartan

Substances

Aldehydes
Angiotensin II Type 1 Receptor Blockers
Angiotensins
Insulin
Membrane Glycoproteins
Membrane Transport Proteins
Phosphoproteins
Tetrazoles
Angiotensin II
Valsartan
8-Hydroxy-2'-Deoxyguanosine
Cybb protein, rat
NADPH Oxidase 2
NADPH Oxidases
CYBA protein, human
Deoxyguanosine
Valine
4-hydroxy-2-nonenal