Endocrine and genotoxic functions of glucose: Potential link to two types of human aging pathology

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

An increase in chronic «glycemic load» is characteristic for modern times. Among plentiful of glucose functions two principal can be emphasized: first, endocrine (in particular, ability to induce insulin secretion) and second, DNA-damaging related to formation of reactive oxygen species (ROS). It was suggested by us earlier that a shift in the ratio of mentioned functions reflects a possible “joker" role of glucose as an impor­tant modifier of human pathology. Therefore, we embarked on a study to investigate an individual effect of peroral glucose challenge on serum insulin level and ROS generation by mononuclears (luminol-depend- ent/latex-induced chemiluminescence) in a 20 healthy people in age 28-75. Concentrations of glucose, blood lipids, carbonylated proteins, malondialdehyde, leptin and TNF-alpha were determined as well. On the basis of received data two separate groups could be distinguished: one (n=8), in which glucose stimulation of ROS generation by mononuclears was increased and relatively prevailed over induction of insulin secretion (state of so called glucose-induced genotoxicity, GIGT), and another (n=12), in which signs of GIGT were not revealed. People who belonged to the first group were characterized with a tendency to lower body mass index, blood leptin and cholesterol and to higher TNF concentration. Thus, if joker function of glucose is real­ized in «genotoxic mode», the phenotype (and probably genotype) of probands may be rather distinctive to the one discovered in glucose-induced «endocrine prevalence». Whether such changes may serve as a pro- mutagenic or pro-endocrine basis for the rise of different chronic diseases or, rather, different features/aggressiveness of the same disease warrants further study.

About the authors

L. М. Berstein

N.N. Petrov Institute of Oncology

Author for correspondence.
Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

D. A. Vasilyev

N.N. Petrov Institute of Oncology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

Т. Е. Poroshina

N.N. Petrov Institute of Oncology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

I. G. Kovalenko

N.N. Petrov Institute of Oncology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

S. A. Malisheva

N.N. Petrov Institute of Oncology

Email: shabanov@mail.rcom.ru
Russian Federation, St. Petersburg

References

  1. Берштейн Л. М. Онкоэндокринология: традиции, настоящее и перспективы. СПб.: Наука, 2004. 343 с.
  2. Берштейн Л. М. Джокерная роль глюкозы в развитии основных неинфекционных заболеваний // Вести. РАМН. 2005. № 2. С. 48-51.
  3. Берштейн Л. М., Квачевская Ю. О., Гамаюнова В. Б. и др. Метаболический синдром инсулинорезистентности и его последствия при раке тела матки // Мед. акад. журн. 2001. Т. 1. № 2. С. 45-54.
  4. Дильман В. М. Четыре модели медицины. Л.: Медицина, 1987. 287 с.
  5. Киселев В. И., Ляшенко А. А. Молекулярные механизмы регуляции гиперпластических процессов. М.: Димитрейд График Групп, 2005. 364 с.
  6. Климов А. Н., Нагорнев В. А. Эволюция холестериновой концепции атерогенеза: от Аничкова до наших дней // Мед. акад. журн. 2001. Т. 1. № 3. С. 23-32.
  7. Ледвина М. Определение 0-липопротеидов сыворотки турбидиметрическим методом // Лаб. дело. 1960. № 3. С. 13-17.
  8. Andreassi М. G., Botto N. DNA damage as a new emerging risk factor in atherosclerosis // Trends. Cardiovasc. Med. 2003. Vol. 13. P. 270-275.
  9. Basu R., Breda E., Oberg R. L. et al. Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance // Diabetes. 2003. Vol. 52. P. 1738-1748.
  10. Berstein L. M., Tsyrlina E. V., Vasilyev D. A. etal. Phenomenon of the switching of estrogen effects and joker function of glucose: similarities, relation to age-associated pathology, approaches to correction // Ann. New York Acad. Sci. 2005. Vol. 1057. P. 236-246.
  11. Bouche C., Serdy S., Kahn C. R., Goldfine A. B. The cellular fate of glucose and its relevance in type 2 diabetes // Endocr. Rev. 2004. Vol. 25. P. 807-830.
  12. Braga Р. С., Sala М. Т., Dal Sasso М. et al. Influence of age on oxidative burst (chemiluminescence) of polymorphonuclear neutrophil leukocytes // Gerontology. 1998. Vol. 44. P. 192-197.
  13. Brand-Miller J. C. Glycemic load and chronic disease // Nutr. Rev. 2003. Vol. 61 (Pt. 2). P. S49-S55.
  14. Ceriello A., Hanefeld M., Leiter L. et al. Post¬prandial glucose regulation and diabetic complications // Arch. Intern. Med. 2004. Vol. 164. P. 2090-2095.
  15. Ceriello A., Quatraro A., Giugliano D. Diabetes mellitus and hypertension: the possible role of hyperglycaemia through oxidative stress H Diabetologia. 1993. Vol. 36. P. 265-266.
  16. Dandona P., Mohanty P, Ghanim H. et al. The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation H J. Clin. Endocrinol. Metabol. 2001. Vol. 86. P. 355-362.
  17. Dandona P, Thusu K., Cook S. et al. Oxidative damage to DNA in diabetes mellitus II Lancet. 1996. Vol. 347. P. 444-445.
  18. Dandona P., Thusu K., Hafeez R. et al. Effect of hydrocortisone on oxygen free radical generation by mononuclear cells // Metabolism. 1998. Vol. 47. P. 788-791.
  19. Droge IV. Free radicals in the physiologic control of cell function H Physiol. Rev. 2002. Vol. 82. P. 47-95.
  20. Fernandez-Real J. M., Ricart HI Insulin resistance and chronic cardiovascular inflammatory syndrome // Endocrine Rev. 2003. Vol. 24. P. 278-301.
  21. Ferrannini E., Gastaldelli A., Miyazaki Y. et al. Р-Cell Function in Subjects Spanning the Range from Normal Glucose Tolerance to Overt Diabetes: A New Analysis H J. Clin. Endocrinol. Metabol. 2005. Vol. 90. P. 493-500.
  22. Furukawa S., Fujita T, Shimabukuro M. et al. Increased oxidative stress in obesity and its impact on metabolic syndrome // J. Clin. Invest. 2004. Vol. 114. P. 1752-1761.
  23. Haffner S. M. The importance of hyperglycemia in nonfasting state to the development of cardio-vascular disease H Endocr. Rev. 1998. Vol. 19. P. 583-592.
  24. Jayshree R. S., Ganguli N. K., Dubey M. L. et al. Generation of reactive oxygen species by blood monocytes during acute Plasmodium knowlesi infection in rhesus monkeys // APMIS. 1993. Vol. 101. P. 762-766.
  25. Levine R. L., Garland C. N., Oliver C. N. Determination of carbonyl content in oxidatively modified proteins // Methods Enzymol. 1990. Vol. 186. P. 464-478.
  26. Liehr J. G. Dual role of oestrogens as hormones and procarcinogens: tumour initiation by metabolic activation of oestrogens H Eur. J. Cancer Prev. 1997. Vol. 6. P. 3-10.
  27. Lin Y, Berg A. H., Iyengar P et al. The hyperglycemia-induced inflammatory response in adipocytes: the role of reactive oxygen species H J. Biol. Chern. 2005. Vol. 280. P. 4617^4626.
  28. Matthews D. R., HoskerJ. P, Rudenski A. S. et al. Homeostasis model assessment: insulin resistance and P-cell function from fasting plasma glucose and insulin concentration in man I/ Diabetologia. 1985. Vol. 28. P.412419.
  29. Mohanty P, Hamouda IV., Garg R. etal. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes // J. Clin. Endocrinol. Metabol. 2000. Vol. 85. P. 2970-2973.
  30. Okhawa H., Ohishi N., Yagi K. Reaction of lipid peroxides with thiobarbituric acid // J. Lipid. Res. 1978. Vol. 19. P. 1053-1057.
  31. Reaven G. Pathophysiology of insulin resistance in human disease H Physiol. Rev. 1995. Vol. 75. P. 473-186.
  32. Santen R. J. Endocrine-responsive cancer // Williams textbook of endocrinology / P. R. Larsen et al., eds. Philadelphia: W. B. Saunders Comp., 2003. P. 1797-1833.
  33. Schinner S.. Scherbaum W. A., Bornstein S. R.. Barthel A. Molecular mechanisms of insulin resistance И Diabet. Med. 2005. Vol. 22. P. 674-682.
  34. Silvera S. A., Jain M.. Howe G. R. et al. Dietary carbohydrates and breast cancer risk: A prospective study of the roles of overall glycemic index and glycemic load H Int. J. Cancer. 2005. Vol. 114. P. 653-658.
  35. United Nations. World Population Aging: 1950- 2050. UN Publications, DESA, Population Division. NY: UN, 2001. [http:/www. un.org/esa/ population/publications/worldageingl 9502050]
  36. Vlassara H., Cai IV, Crandall J. et al. Inflammatory mediators are induced by dietary' glycotoxins, a major risk factor for diabetic angiopathy // Proc. Natl. Acad. Sci. (USA) 2002. Vol. 99. P. 15596-15601.
  37. Zimmet P The burden of type 2 diabetes: are we doing enough? // Diabetes Metab. 2003. Vol. 29 (Pt. 2). P. S9-S18.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2006 Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.