Zhu Bin, Gong Yuewen, Chen Pengmin, Zhang Haojun, Zhao Tingting, Li Ping
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Mol Cell Biochem. 2014 Aug;393(1-2):23-32. doi: 10.1007/s11010-014-2043-1. Epub 2014 Mar 28.
DNase I is an endonuclease responsible to destruction of chromatin during apoptosis. However, its role in diabetes is still unclear. With blood samples from our previous study related to type 2 diabetes, we examined the DNase I activity in the serum of these patients and the role of DNase I in the injury of pancreas was further investigated in rats and INS-1 cells. Serum and pancreatic tissues from human and rats were used for the study. Insulin resistance and diabetes were induced by high fat diet and STZ injection, respectively. DNase I activity was determined by radial enzyme-diffusion method. Expressions of DNase I and caspase-3 in pancreas were determined in rat pancreatic tissues and INS-1 cells. Apoptosis of INS-1 cells was determined by both TUNEL assay and Flow Cytometry. There was a significant elevation of DNase I activity in serum of patients with type 2 diabetes and rats with STZ injection. Moreover, increase in DNase I expression was observed in the pancreas of diabetic person and rats. Furthermore, high glucose induced both DNase I and caspase-3 expression and at the same time increased apoptosis rate of INS-1 cells. In conclusion, elevated DNase I in diabetes may be related to pancreatic injury and could be one of the causes that induce diabetes.
脱氧核糖核酸酶I(DNase I)是一种核酸内切酶,负责在细胞凋亡过程中破坏染色质。然而,其在糖尿病中的作用仍不清楚。利用我们之前与2型糖尿病相关研究中的血样,我们检测了这些患者血清中的DNase I活性,并在大鼠和INS-1细胞中进一步研究了DNase I在胰腺损伤中的作用。使用来自人和大鼠的血清及胰腺组织进行研究。分别通过高脂饮食和注射链脲佐菌素(STZ)诱导胰岛素抵抗和糖尿病。通过放射酶扩散法测定DNase I活性。在大鼠胰腺组织和INS-1细胞中测定胰腺中DNase I和半胱天冬酶-3(caspase-3)的表达。通过TUNEL检测法和流式细胞术测定INS-1细胞的凋亡。2型糖尿病患者和注射STZ的大鼠血清中的DNase I活性显著升高。此外,在糖尿病患者和大鼠的胰腺中观察到DNase I表达增加。此外,高糖诱导DNase I和caspase-3表达,同时增加INS-1细胞的凋亡率。总之,糖尿病中DNase I升高可能与胰腺损伤有关,并且可能是诱发糖尿病的原因之一。