Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

被引：7

作者：

Kejariwal D. ^{[1
]}

Stepien K.M. ^{[2
]}

Smith T. ^{[3
]}

Kennedy H. ^{[1
]}

Hughes D.A. ^{[3
]}

Sampson M.J. ^{[2
]}

机构：

[1] Department of Gastroenterology, Norfolk and Norwich University Hospital, Norwich NR4 7UY, Colney Lane

[2] Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospital

[3] Institute of Food Research, Norwich Research Park, Colney

来源：

BMC Endocrine Disorders | / 8卷 / 1期

关键词：

Metformin; Telomere Length; Colonic Mucosa; Mean Fluorescent Intensity; Hank Balance Salt Solution;

D O I：

10.1186/1472-6823-8-12

中图分类号：

学科分类号：

摘要：

Background: Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods: We examined telomere length (by flow fluorescent in situ hybridization) and oxidative DNA damage (flow cytometry of 8 - oxoguanosine) in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9%) and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results: Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5). Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7). There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1). Conclusion: Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism. © 2008 Kejariwal et al; licensee BioMed Central Ltd.

引用

共 30 条

[21]

Halliwell B., Gutteridge J.M.C., Free Radicals in Biology and Medicine, (1999)

[22]

Leinonen J., Lehtimaki T., Toyokuni S., Okada K., Tanaka T., Hiai H., Ochi H., Laippala P., Rantalaiho V., Wirta O., Pasternack A., Alho H., New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus, FEBS Lett, 417, pp. 150-152, (1997)

[23]

Demissie S., Levy D., Benjamin E.J., Cupples L.A., Gardner J.P., Herbert A., Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study, Aging Cell, 5, pp. 325-330, (2006)

[24]

Adaikalakoteswari A., Balasubramanyam M., Mohan V., Telomere shortening occurs in Asian Indian type 2 diabetic patients, Diabetic Med, 22, pp. 1151-1156, (2005)

[25]

Spyridopoulos I., Haendeler J., Urbrich C., Brummendorf T.H., Oh H., Schneider M.D., Zeiher A.M., Dimmeler S., Statins enhance migratory capacity by upregulation of the telomere repeat binding factor TRF-2 in endothelial progenitor cells, Circulation, 110, pp. 3136-3142, (2004)

[26]

Brouilette S.W., Moore J.S., McMahon A.D., Thompson J.R., Ford I., Shepherd J., Packard C.J., Samani N.J., West of Scotland Coronary Prevention Study Group. Telomere length, risk of coronary heart disease, a statin treatment in the West of Scotland Primary Prevention Study: A nested case-control study, Lancet, 369, 9556, pp. 107-114, (2007)

[27]

Markowitz S.D., Aspirin and colon cancer - Targeting prevention?, N Engl J Med, 356, 21, pp. 2195-2198, (2007)

[28]

Mira M.L., Silva M.M., Queiroz M.J., Manso C.F., Angiotensin converting enzyme inhibitors as oxygen free radical scavengers, Free Radic Res Commun, 19, 3, pp. 173-181, (1993)

[29]

Scribner A.W., Loscalzo J., Napoli C., The effect of angiotensin-converting enzyme inhibition on endothelial function and oxidant stress, Eur J Pharmacol, 482, pp. 95-99, (1997)

[30]

Khaw K.T., Wareham N., Bingham S., Luben R., Welch A., Day N., Preliminary communication: Glycated hemoglobin, diabetes, and incident colorectal cancer in men and women: A prospective analysis from the European prospective investigation into cancer-Norfolk study, Cancer Epidemiol Biomarkers Prev, 13, 6, pp. 915-919, (2004)

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