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Rev Diabet Stud, 2010, 7(1):15-25 DOI 10.1900/RDS.2010.7.15

Oxidative Stress, Nitric Oxide, and Diabetes

Dario Pitocco1,2, Francesco Zaccardi1,2, Enrico Di Stasio3, Federica Romitelli3, Stefano A. Santini3, Cecilia Zuppi3, Giovanni Ghirlanda1

1Institute of Internal Medicine, Catholic University of Rome, Largo Agostino Gemelli 8, 00168 Rome, Italy
2Contributed equally to the article
3Department of Biochemistry, Catholic University of Rome, 00168 Rome, Italy
Address correspondence to: Dario Pitocco, e-mail:

Manuscript submitted November 6, 2009; resubmitted January 11, 2010; accepted January 27, 2010.

Keywords: type 2 diabetes, diet, lifestyle, nutrition, physical activity, weight loss, glycemic control


In the recent decades, oxidative stress has become focus of interest in most biomedical disciplines and many types of clinical research. Increasing evidence from research on several diseases show that oxidative stress is associated with the pathogenesis of diabetes, obesity, cancer, ageing, inflammation, neurodegenerative disorders, hypertension, apoptosis, cardiovascular diseases, and heart failure. Based on this research, the emerging concept is that oxidative stress is the “final common pathway”, through which risk factors of several diseases exert their deleterious effects. Oxidative stress causes a complex dysregulation of cell metabolism and cell-cell homeostasis. In this review, we discuss the role of oxidative stress in the pathogenesis of insulin resistance and beta-cell dysfunction. These are the two most relevant mechanisms in the pathophysiology of type 2 diabetes, and in the pathogenesis of diabetic vascular complications, the leading cause of death in diabetic patients.

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Epigenetic manifestation of metabolic syndrome and dietary management

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Role of forkhead transcription factors in diabetes-induced oxidative stress

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