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Journal of Diabetes Research
Volume 2013, Article ID 134395, 8 pages
http://dx.doi.org/10.1155/2013/134395
Research Article

The Role of Adrenomedullin in the Renal NADPH Oxidase and (Pro)renin in Diabetic Mice

1Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
2Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

Received 4 February 2013; Accepted 25 June 2013

Academic Editor: Bernard Portha

Copyright © 2013 Michio Hayashi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Adrenomedullin has an antioxidative action and protects organs in various diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we investigated the NADPH oxidase expression, renin-secreting granular cell (GC) hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)-induced diabetic adrenomedullin gene knockout (AMKO) mice compared with the STZ-diabetic wild mice at 10 weeks. The NADPH oxidase p47phox expression and lipid peroxidation products were enhanced in the glomeruli of the diabetic mice compared with that observed in the controls in both wild and AMKO mice. These changes were more obvious in the AMKO mice than in the wild mice. Glomerular mesangial matrix expansion was more severe in the diabetic AMKO mice than in the diabetic wild mice and exhibited a positive correlation with the degree of lipid peroxidation products in the glomeruli. Proteinuria was significantly higher in the diabetic AMKO mice than in the diabetic wild mice. The GC hyperplasia score and the renal prorenin expression were significantly increased in the diabetic AMKO mice than in the diabetic wild mice, and a positive correlation was observed with the NADPH oxidase expression in the macula densa. The endogenous adrenomedullin gene exhibits an antioxidant action via the inhibition of NADPH oxidase probably by suppressing the local renin-angiotensin system.