Response to Comment on Balestrieri et al. Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment. Diabetes 2015;64:1395–1406

Diabetes, Apr 2015

Maria Luisa Balestrieri, Maria Rosaria Rizzo, Michelangela Barbieri, Pasquale Paolisso, Nunzia D’Onofrio, Alfonso Giovane, Luigi Servillo, Giuseppe Paolisso, Raffaele Marfella

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Response to Comment on Balestrieri et al. Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment. Diabetes 2015;64:1395–1406

Sir tuin 6 Expression and Inflammator y Activit y in Diabetic Atherosclerotic Plaques: Ef fects of Incretin Treatment. Diabetes 2015;64:1395-1406 Maria Luisa Balestrieri 1 Maria Rosaria Rizzo 0 Michelangela Barbieri 0 Pasquale Paolisso 0 Nunzia D'Onofrio 1 Alfonso Giovane 1 Luigi Servillo 1 Giuseppe Paolisso 0 Raffaele Marfella 0 0 Department of Medical , Surgical, Neurological , Aging and Metabolic Sciences, Second University of Naples , Naples , Italy 1 Department of Biochemistry, Biophysics and General Pathology, Second University of Naples , Naples , Italy RESPONSE TO COMMENT ON BALESTRIERI ET AL. Duality of Interest. No potential conflicts of interest relevant to this article were reported. - We agree with Yu and Sun (1) that sirtuin 6 (SIRT6) was not only implicated in the repression of inflammation (2), oxidative stress, tumor, and aging (3) but also functioned as an oncogene in the epidermis (4). The idea that SIRT6 is a two-edged sword in health and disease is nevertheless intriguing. SIRT6 promotes resistance to DNA damage and oxidative stress, the principal defects associated with age-related diseases. The modulation of aging and other metabolic functions by SIRT6 may be indicative of previously unrecognized regulatory systems in the cell (5). In line to such evidence, we unveiled SIRT6 as a possible target for the antiatherogenic therapies (6). By maintaining both the integrity and the expression of the mammalian genome, SIRT6 may help prevent cellular senescence. Moreover, successful molecular modulation of SIRT6 activity may lead to the development of new chemotherapeutic modalities as well as the development of new therapeutic strategies to delay atherosclerosis progression in high-risk patients, such as patients with diabetes. 1. Yu W-L , Sun Y. Comment on Balestrieri et al. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment . Diabetes 2015 ; 64 : 1395 - 1406 (Letter). Diabetes 2015 ; 64 :e5. DOI: 10.2337/ db14- 1633 2. Zhang P , Tu B , Wang H , et al. Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion . Proc Natl Acad Sci U S A 2014 ; 111 : 10684 - 10689 3. Sun H , Wu Y , Fu D , Liu Y , Huang C. SIRT6 regulates osteogenic differentiation of rat bone marrow mesenchymal stem cells partially via suppressing the nuclear factor-kB signaling pathway . Stem Cells 2014 ; 32 : 1943 - 1955 4. Ming M , Han W , Zhao B , et al. SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer . Cancer Res 2014 ; 74 : 5925 - 5933 5. Beauharnois JM , Bolvar BE , Welch JT . Sirtuin 6: a review of biological effects and potential therapeutic properties . Mol Biosyst 2013 ; 9 : 1789 - 1806 6. Balestrieri ML , Rizzo MR , Barbieri M , et al. Sirtuin 6 expression and inflammatory activity in diabetic atherosclerotic plaques: effects of incretin treatment . Diabetes 2015 ; 64 : 1395 - 1406


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Maria Luisa Balestrieri, Maria Rosaria Rizzo, Michelangela Barbieri, Pasquale Paolisso, Nunzia D’Onofrio, Alfonso Giovane, Luigi Servillo, Giuseppe Paolisso, Raffaele Marfella. Response to Comment on Balestrieri et al. Sirtuin 6 Expression and Inflammatory Activity in Diabetic Atherosclerotic Plaques: Effects of Incretin Treatment. Diabetes 2015;64:1395–1406, Diabetes, 2015, e6-e6, DOI: 10.2337/db14-1676