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

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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 β-cell damage.

Original languageEnglish
Pages (from-to)927-933
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume332
Issue number4
DOIs
Publication statusPublished - Jul 15 2005

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Oxidative stress
NADPH Oxidase
Medical problems
Type 2 Diabetes Mellitus
Animals
Oxidative Stress
Animal Models
Valsartan
Inbred OLETF Rats
Angiotensin II Type 1 Receptor Blockers
Deoxyguanosine
Angiotensin II
Oral Administration
Rats
Cells
Insulin
Staining and Labeling
Proteins
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist. / Nakayama, Mieko; Inoguchi, Toyoshi; Sonta, Toshiyo; Maeda, Yasutaka; Sasaki, Shuji; Sawada, Fumi; Tsubouchi, Hirotaka; Sonoda, Noriyuki; Kobayashi, Kunihisa; Sumimoto, Hideki; Nawata, Hajime.

In: Biochemical and Biophysical Research Communications, Vol. 332, No. 4, 15.07.2005, p. 927-933.

Research output: Contribution to journalArticle

Nakayama, Mieko ; Inoguchi, Toyoshi ; Sonta, Toshiyo ; Maeda, Yasutaka ; Sasaki, Shuji ; Sawada, Fumi ; Tsubouchi, Hirotaka ; Sonoda, Noriyuki ; Kobayashi, Kunihisa ; Sumimoto, Hideki ; Nawata, Hajime. / Increased expression of NAD(P)H oxidase in islets of animal models of Type 2 diabetes and its improvement by an AT1 receptor antagonist. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 332, No. 4. pp. 927-933.
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