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糖尿病中脱氧核糖核酸酶I活性增加可能与胰腺损伤有关。

Increased DNase I activity in diabetes might be associated with injury of pancreas.

作者信息

Zhu Bin, Gong Yuewen, Chen Pengmin, Zhang Haojun, Zhao Tingting, Li Ping

机构信息

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

出版信息

Mol Cell Biochem. 2014 Aug;393(1-2):23-32. doi: 10.1007/s11010-014-2043-1. Epub 2014 Mar 28.

Abstract

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.

摘要

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。

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