DNase I aggravates islet β-cell apoptosis in type 2 diabetes.

Zhu B¹, Zhang L², Zhang YY³, Wang L⁴, Li XG¹, Liu T¹, Fu YK¹, Zheng YF⁴, Li P⁵, Zhao ZG¹.

Author information

1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.2Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.3Department of Chinese Medicine, Beijing Hepingli Hospital, Beijing 100013, P.R. China.4Department of Chinese Medicine, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing 100050, P.R. China.5Department of Nephrology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China.

Abstract

Deoxyribonuclease I (DNase I) is an endonuclease responsible for the destruction of chromatin during apoptosis. However, its role in diabetes remains unclear. The aim of the current study was to investigate the role of DNase I combined with high glucose levels in β‑cell apoptosis. Human samples were collected and the DNase I activity was examined. High glucose‑cultured INS‑1 cells were transfected with DNase I small interfering RNA (siRNA) and the cell apoptosis was examined by western blotting and flow cytometry. Cell viability was analyzed by the Cell Counting Kit‑8 assay. Cell apoptosis resulting from 50 mU/µl DNase I was also observed by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick‑end labeling stain and western blotting. Compared with healthy controls, the serum DNase I activity of patients with diabetes was significantly increased (P<0.05). In addition, DNase I expression was observed to be significantly increased in human pancreatic tissues. The addition of high glucose upregulated the cell apoptotic rate, whereas DNase I knockdown significantly reduced apoptosis in cells treated with high glucose. In addition, the western blotting results indicated that caspase‑3 was increased subsequent to treatment of cells with 30 mM high glucose, however, this increase can be reversed by transfection with DNase I siRNA (P<0.05). Compared with cells cultured in normal conditions and high glucose, 50 mU/µl DNase I was able to significantly increase the cell apoptotic rate and level of caspase-3. DNase I activity was observed to be increased in type 2 diabetes, and high glucose combined with increased DNase I is suggested to aggravate β-cell apoptosis.