The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications
Oxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic va...
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2012-08-01
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| Series: | Diabetes & Metabolism Journal |
| Subjects: | |
| Online Access: | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-36-255.pdf |
| _version_ | 1828340464660512768 |
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| author | Shuji Sasaki Toyoshi Inoguchi |
| author_facet | Shuji Sasaki Toyoshi Inoguchi |
| author_sort | Shuji Sasaki |
| collection | DOAJ |
| description | Oxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic vascular tissues. The mechanisms underlying activation and up-regulation of NAD(P)H oxidase has been supposed to be mediated by high glucose-induced protein kinase C (PKC) activation. In this review article, activation of local renin-angiotensin II system induced by chymase activation is also shown to amplify such a PKC-dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the beneficial effect of antioxidants on diabetic vascular complications. Bilirubin has been recognized as a strong endogenous antioxidant. Here markedly lower prevalence of vascular complications is shown in diabetic patients with Gilbert syndrome, a congenital hyperbilirubinemia, as well as reduced markers of oxidative stress and inflammation. Lastly, statin, angiotensin II receptor blocker, chymase inhibitor, bilirubin and biliverdin, PKC β isoform inhibitor, and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have some beneficial effect on diabetic vascular complications, via inhibiting PKC-NAD(P)H oxidase activation, supporting the notion that this mechanism may be an effective therapeutic target for preventing diabetic vascular complications. |
| first_indexed | 2024-04-13T22:56:58Z |
| format | Article |
| id | doaj.art-bc55d9a1ee894bd69c931438c0acd002 |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-04-13T22:56:58Z |
| publishDate | 2012-08-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-bc55d9a1ee894bd69c931438c0acd0022022-12-22T02:25:59ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872012-08-0136425526110.4093/dmj.2012.36.4.2552412The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular ComplicationsShuji SasakiToyoshi InoguchiOxidative stress has been paid increasing attention to as an important causative factor for diabetic vascular complications. Among possible various sources, accumulating evidence has indicated that NAD(P)H oxidase may be the most important source for reactive oxygen species production in diabetic vascular tissues. The mechanisms underlying activation and up-regulation of NAD(P)H oxidase has been supposed to be mediated by high glucose-induced protein kinase C (PKC) activation. In this review article, activation of local renin-angiotensin II system induced by chymase activation is also shown to amplify such a PKC-dependent activation of NAD(P)H oxidase. Additionally, human evidence showing the beneficial effect of antioxidants on diabetic vascular complications. Bilirubin has been recognized as a strong endogenous antioxidant. Here markedly lower prevalence of vascular complications is shown in diabetic patients with Gilbert syndrome, a congenital hyperbilirubinemia, as well as reduced markers of oxidative stress and inflammation. Lastly, statin, angiotensin II receptor blocker, chymase inhibitor, bilirubin and biliverdin, PKC β isoform inhibitor, and glucagon-like peptide-1 analog, are shown to serve as antioxidants and have some beneficial effect on diabetic vascular complications, via inhibiting PKC-NAD(P)H oxidase activation, supporting the notion that this mechanism may be an effective therapeutic target for preventing diabetic vascular complications.http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-36-255.pdfAngiotensin IIBilirubinChymasesNADPH oxidaseOxidative stressProtein kinase C |
| spellingShingle | Shuji Sasaki Toyoshi Inoguchi The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications Diabetes & Metabolism Journal Angiotensin II Bilirubin Chymases NADPH oxidase Oxidative stress Protein kinase C |
| title | The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications |
| title_full | The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications |
| title_fullStr | The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications |
| title_full_unstemmed | The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications |
| title_short | The Role of Oxidative Stress in the Pathogenesis of Diabetic Vascular Complications |
| title_sort | role of oxidative stress in the pathogenesis of diabetic vascular complications |
| topic | Angiotensin II Bilirubin Chymases NADPH oxidase Oxidative stress Protein kinase C |
| url | http://e-dmj.org/Synapse/Data/PDFData/2004DMJ/dmj-36-255.pdf |
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