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糖尿病通过增加大鼠糖酵解酶的活性促进背内侧下丘脑(DMH)诱导的结直肠癌。

Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats.

作者信息

Jia Yanglei, Xu Gang, Zhou Wenjing, Wang Zhenzheng, Meng Linlin, Zhou Songnan, Xu Xia, Yuan Huiqing, Tian Keli

机构信息

Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, China.

Department of Gastroenterology, 456 Hospital of PLA, Jinan, Shandong, China.

出版信息

PLoS One. 2014 Oct 17;9(10):e110455. doi: 10.1371/journal.pone.0110455. eCollection 2014.

Abstract

The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.

摘要

本研究的目的是探讨糖尿病与结直肠癌发生之间的关联以及这种相互作用所涉及的可能机制。采用低剂量链脲佐菌素(STZ)诱导糖尿病大鼠模型,随后给予低剂量二甲基肼(DMH)诱导结直肠癌。测量结肠中异常隐窝灶(ACF)的形成以及肿瘤的发生率、数量和大小。还测量了结肠组织中糖酵解酶的活性。结果表明,糖尿病大鼠的ACF总数以及含有不同数量隐窝的病灶数量均增加。在实验治疗结束时,糖尿病大鼠的肿瘤发生率、数量和大小也增加。总体而言,这些数据表明糖尿病增加了结直肠癌的风险。糖尿病大鼠结肠组织中己糖激酶(HK)和丙酮酸激酶(PK)的活性增加,而丙酮酸脱氢酶(PDH)的活性降低。此外,这些酶在肿瘤内的活性高于肿瘤周围。这些数据表明,高糖酵解率可能在糖尿病大鼠的结直肠癌发生中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7761/4201553/e47533ce93fe/pone.0110455.g001.jpg

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