Rational Pharmacotherapy in Cardiology

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Insulin resistance plays the main role in the pathogenesis of diabetes mellitus and its complications. It is also a major factor of the pathology associated with age, which leads to accelerated aging. Data about the role of insulin resistance and its correction in vascular aging are presented.

About the Authors

E. N. Dudinskaya
State Research Centre for Preventive Medicine, Moscow
Russian Federation

O. N. Tkacheva
State Research Centre for Preventive Medicine, Moscow
Russian Federation

I. D. Strazhesko
State Research Centre for Preventive Medicine, Moscow
Russian Federation

D. U. Akasheva
State Research Centre for Preventive Medicine, Moscow
Russian Federation


1. Shestakova M.V., Breskina O.Ju. Insulin resistance: pathophysiology, clinical symptoms, treatment. Saharnyj diabet 2002; 4(10): 523–27. Russian (Шестакова М.В., Брескина О.Ю. Инсулинорезистентность: патофизиология, клинические проявления, подходы к лечению. Сахарный диабет 2002; 4(10): 523–27).

2. Kononenko I. V., Smirnova O. M. Insulin resistanceand its correction in T2DM. Lechashhij vrach 2006; 2: 18–2. Russian (Кононенко И.В., Смирнова О.М. Инсулинорезистентность и пути ее коррекции при сахарном диабете 2 типа. Лечащий врач 2006; 2: 18–2).

3. Hollenbeck CB, Haskell W, Rosenthal M, Reaven GM. Effect of habitual physical activity on regulation of insulin-stimulated glucose disposal in older males. J Am Geriatr Soc 1984; 33:273–77.

4. Matthaei S., Stumvoll M., Kellerer M. Pathophysiology and pharmacological treatment of insulin resistance. Endocrine reviews 2006; 21(6): 585–18.

5. Reaven G.M. Role of insulin resistance in human disease. Diabetes 1988; 37:1595—607.

6. Ametov A. S. Insulin secretion in normal and in T2DM. Saharnyj diabet 2007 (4): 11–6. Russian (Аметов А.С. Секреция инсулина в норме и при сахарном диабете 2 типа. Сахарный диабет 2007 (4): 11–6).

7. Borona E., Kiechl S., Willeit J. et al. Prevalence of Insulin resistance in metabolic disorders. The Brunneck Study. Diabetes 1998;47: 1643–648.

8. Balabolkin M. I. Insulin resistance and its rople in T2DM. Saharnyj diabet 2002; (1): 12–0. Russian (Балаболкин М.И. Инсулинорезистентность и ее значение в патогенезе нарушений углеводного обмена и сахарного диабета типа 2. Сахарный диабет 2002; (1): 12–0).

9. Demidova T. Yu. Etiopathogenic role of insulin resistance in the development of metabolic and vascular disorders in T2DM. Farmateka 2010;16: 18–4. Russian (Демидова Т. Ю. Этиопатогенетическая роль инсулинорезистентности в развитии метаболических и сосудистых нарушений при сахарном диабете 2 типа. Фарматека 2010; 16: 18–4).

10. Gardner DG, Shobeck D, eds., Greenspan's Basic and Clinical Endocrinology, 8th ed. New York: Mc-Graw-Hill; 2007.

11. Nikonova T. V., Pekareva E. V., Dedov I. I. The functional activity of β-cells and peripheral insulin resistance in patients with different variants of the beginning of diabetes. Saharnyj diabet 2012;(3):24– 26. Russian (Никонова Т.В., Пекарева Е.В., Дедов И.И. Функциональная активность β-клеток и периферическая инсулинорезистентность у пациентов с различными вариантами дебюта сахарного диабета. Сахарный диабет 2012;(3):24–6).

12. Andres R. Aging and diabetes. Med Clin North Am 1971; 55:835–46.

13. Shimokata H, Muller DC, Fleg JL, et al. Age as independent determinant of glucose tolerance. Diabetes 1991;40: 44–1.

14. Maneatis T, Condie R, Reaven GM. Effect of age on plasma glucose and insulin responses to a test mixed meal. J Am Geriatr Soc 1982;30:178–82.

15. Seals DR, Hagberg JM, Allen WK. Glucose tolerance in young and older athletes and sedentary men. J Appl Physiol 1984; 56:1521–525.

16. Rosenthal M, Doberne L, Greenfield MS, et al. Effect of age on glucose tolerance, insulin secretion, and in vivo insulin action. J Am Geriatr Soc 1981; 30:562–76

17. Szoke E, Shrayyef MZ, Messing S. Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell function in individuals with impaired glucose tolerance. Diabetes Care 2008; 31(3):539– 43.

18. Imbeault P, Prins JB, Stolic M et al. Aging per se does not influence glucose homeostasis. Diabetes Care 2003; 26:480–.

19. Iozzo P, Beck-Nielsen H, Laasko M, Smith U. Independent influence of age on basal insulin secretion in nondiabetic humans: European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab 1999; 84: 863–68.

20. Chang AM, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab 2003; 284(1): E7–12

21. Jones CNO, Pei D, Sturis J, et al. Identification of an age-related defect in glucose-stimulated insulin secretion in non-diabetic women. Endocrinol & Metab 1999; 4:193–00.

22. Paolisso G, Barbieri M, Rizzo MR et al. Low insulin resistance and preserved beta-cell function contribute to human longevity but are not associated with TH-INS genes. Exp Gerontol 2001; 37:149– 156.

23. Barbieri M, Rizzo MR, Manzella D. Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol 2003; 38: 137–43.

24. Strazhesko I. D., Akasheva D. U., Dudinskaya E. N., Tkacheva O. N. Aging vessels: main features and mechanisms. Kardiovaskuljarnaja terapija i profilaktika 2012; 11 (4): 93–00. Russian (Стражеско И. Д., Акашева Д. У., Дудинская Е. Н., Ткачева О.Н. Старение сосудов: основные признаки и механизмы. Кардиоваскулярная терапия и профилактика 2012; 11 (4): 93–00).

25. Allsopp R.C. Harley C.B. Evidence for a critical telomere length in senescent human fibroblasts. Experimental Cell Research 1995; 219:130–36

26. Bodnar A.G., Ouellette M., Frolkis M., et al. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279: 349–52.

27. LeRoith D, Taylor SI, Olefsky JM. Diabetes Mellitus: A Fundamental and Clinical Text. Philadelphia: Lippincott Williams & Wilkins; 2004.

28. Sampson M.J. Winterbone M.S. Hughes J.C. et al. Monocyte telomere shortening and oxidative DNA damage in type 2 diabetes. Diabetes Care 2006; 29:283–89.

29. Adaikalakoteswari A., Balasubramanyam M., Ravikumar R. et al. Association of telomere shortening with impaired glucose tolerance and diabetic macroangiopathy. Atherosclerosis 2007; 195:83–9.

30. Gardner JP, Li S, Srinivasan SR, et al. Rise in insulin resistance is associated with escalated telomere attrition. Circulation 2005; 111: 2171–177

31. Mulder H. Is shortening of telomeres the missing link between aging and the Type 2 Diabetes epidemic? Aging 2010; 2(10): 634–36.

32. Valdes AM, Andrew T, Gardner JP et al. Obesity, cigarette smoking, and telomere length in women. Lancet 2005; 366: 662–64.

33. Demissie S, Levy D, Benjamin EJ. et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 2006; 5: 325–30.

34. Al-Attas O., Al-Daghri N., Bamakhramah A., et al. Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth. Acta Paediatr 2010; 99:896–99.

35. Daubenmiera J., Linb J., Blackburnb E., Hechta F. Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology 2012; 37(7): 917–28.

36. Evans JL, Maddux BA, Goldfine ID. The molecular basis for oxidative stress-induced insulin resistance. Antioxid Redox Signal 2005;7 (7–):1040–2.

37. Patti M. The Role of Mitochondria in the Pathogenesis of Type 2 Diabetes. Endocr Rev 2010; 31(3): 364–95

38. Phielix E , Szendroedi J , Roden M . Mitochondrial function and insulin resistance during aging: a minireview. Gerontology 2011; 57: 387–96.

39. Morino K, Petersen KF, Dufour S, et al. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 2005;115(12):3587–3.

40. Lanza IR, Sreekumaran Nair K. Regulation of skeletal muscle mitochondrial function: genes to proteins. Acta Physiol (Oxf) 2010;199(4):529–7.

41. Emanuela F, Grazia M, Marco de R et al. Inflammation as a Link between Obesity and Metabolic Syndrome. J Nutr Metab 2012;2012:476380.

42. De Luca C, Olefsky JM. Inflammation and insulin resistance. FEBS Lett 2008; 582 (1) : 97–05.

43. Ahmed N, Thornalley PJ. Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 2007;9(3):233–5.

44. Sun S, Ji Y, Kersten S, Qi L. Mechanisms of Inflammatory Responses in Obese Adipose Tissue. Annu Rev Nutr 2012;32:261–6.

45. Kim J., Montagnani M., Koh K.K., Quon M.J. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006; 113: 888– 904.

46. Kochegura T.N., Akopjan Zh.A., Sharonov G.V. The influence of diabetes mellitus type 2 by the number of circulating progenitor cells in patients with ischemic cardiomyopathy. Saharnyj diabet 2011; 3: 36–3 (Кочегура Т.Н., Акопян Ж.А., Шаронов Г.В. Влияние сопутствующего сахарного диабета 2 типа на количество циркулирующих прогениторных клеток у больных с ишемической кардиомиопатией. Сахарный диабет 2003; 3: 36–3).

47. Baron A.D. Insulin resistance and vascular function. J Diabetes Complications 2002; 16 (1): 92–02.

48. Hughes T. M., Althouse A.D., Niemczyk N. A. Effects of weight loss and insulin reduction on arterial stiffness in the save trial. Cardiovascular Diabetology 2012, 11:114.

49. Makino N, Sasaki M, Maeda T, Mimori K. Telomere biology in cardiovascular disease-role of insulin sensitivity in diabetic hearts. Experimental and clinical cardiology 2010; 15(4):e128–3

50. Facchini F., Hua N., Abbasi F. Insulin resistance as a predictor of age-related diseases. Journal of Clinical Endocrinology & Metabolism; 86(8):3574–578.

51. Hovatta I., de Mello V. D. F., Kananen L. Leukocyte Telomere Length in the Finnish Diabetes Prevention Study. PLoS ONE 2012; 7 (4): e34948.

52. Ryan A. S. Exercise in aging: its important role in mortality, obesity and insulin resistance. Aging health 2010; 6(5): 551–63.

53. Chowanadisai W, Bauerly KA, Tchaparian E, et al. Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC- 1alpha expression. J Biol Chem 2010;285(1):142–2.

54. Spindler SR. Caloric restriction: from soup to nuts. Ageing Res Rev 2010;9(3):324–3

55. Suwa M, Egashira T, Nakano H, Sasaki H, Kumagai S. Metformin increases the PGC-1alpha protein and oxidative enzyme activities possibly via AMPK phosphorylation in skeletal muscle in vivo. J Appl Physiol 2006;101(6):1685–2.

56. Bogacka I, Xie H, Bray GA, Smith SR. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 2005;54(5):1392–

For citation:

Dudinskaya E.N., Tkacheva O.N., Strazhesko I.D., Akasheva D.U. ROLE OF INSULIN RESISTANCE AND ITS CORRECTION IN THE PROCESS OF VASCULAR AGING. Rational Pharmacotherapy in Cardiology. 2013;9(2):163-170. (In Russ.)

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