PHYLOGENESIS, ETIOLOGY AND PATHOGENESIS OF INSULIN RESISTANCE. DIFFERENCES FROM TYPE II DIABETES MELLITUS

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Abstract

We believe that etiological factor of insulin resistance is phylogenetically late formation of insulin and its specific functionality, i.e., providing energy substrates for the biological function of locomotion. According to biological subordination, insulin cannot change regulation formed at the early stages of phylogenesis in all cells, including those that become insulin-dependent at the late stages of phylogenesis. This involves a) β-oxidation of fatty acids in the mitochondria, b) synthesis of С 16:0 palmitic saturated fatty acid, c) glucose metabolism in pro- and eukaryotes, d) regulation of biochemical reactions in insulin-independent cells, e) humoral effects of mediators at the level of paracrine cell communities which are structural and functional units of all internal organs, and f) hormonal regulation at the entire organism level. Pathogenetic factors of insulin resistance are biochemical and functional disorders occurring in vivo upon activation of biological functions and reactions that formed phylogenetically earlier than insulin. During phylogenesis the insulin system has intrinsically built up over the regulatory mechanisms of mitochondria, early unicellular organisms and paracrine cell communities. Insulin functionally interacts with them all, but it cannot abolish the effects of any phylogenetically earlier humoral mediator. Insulin resistance is a pathophysiological disparity between humoral regulation of metabolism at the level of phylogenetically earlier paracrine cell communities and at the level of phylogenetically late total organism, on the one hand, and successive phylogenetic formation of passive cellular uptake of fatty acids as unesterified fatty acids and later triglycerides, on the other. If insulin resistance results from changes in the primary structure of transport proteins, in glucose storage and cellular insulin reception, it can be referred to as type II diabetes mellitus.

 

About the authors

V. N. Titov

Russian Cardiology Research-and-Production Center, Ministry of Health, Moscow, Russia

Author for correspondence.
Email: vn_titov@mail.ru
доктор медицинских наук, профессор, руководитель лаборатории клинической биохимии липидов и липопротеинов ФГБУ «Российский кардиологический научно-производственный комплекс» Минздравсоцразвития России Адрес: 122551, Москва, ул. 3-я Черепковская, д. 15а Тел.: (495) 414-63-10 Russian Federation

References

  1. Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Lechenie saharnogo diabeta i ego oslozhnenij (ruk. dlya vrachej). M.: OAO «Izd-vo «Medicina». 2005. 512 s.
  2. Majorov A.Yu. Insulinorezistentnost’ v patogeneze saharnogo diabeta 2 tipa. Voprosy patogeneza. 2011; 1: 35-43.
  3. Shestakova M.V., Breskina O.Yu. Insulinorezistentnost’: patofiziologiya, klinicheskie proyavleniya, podhody k lecheniyu. Consilium. Med. 2002; 4 (10).
  4. Annuzzi G., De Natale C., Iovine C. et al. Insulin resistance is independently associated with postprandial alterations of triglyceriderich lipoproteins in type 2 diabetes mellitus. Arterioscler. Thromb. Vasc. Biol. 2004; 24: 2397–2402.
  5. Taskinen M.R., Adiels M., Westerbacka J. et al. Dual metabolic defects are reguired to produce hypertriglyceridemia in obese subjects. Arterioscler. Thromb. Vasc. Biol. 2011; 31 (9): 2144–2150.
  6. Riccardi G., Giacco R., Rivellesse A.A. Dietary fat, inslin sensitivity and the metabolic syndrome. Clin. Nutr. 2004; 23 (4): 447–456.
  7. Gof D.C., D’Agostine R.B., Haffner S.M., Otvos J.D. Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the insulin resistance atherosclerosis study. Metabolism. 2005; 54 (2): 264–270.
  8. Stein L.L., Dong M.H., Loomba R. Insulin sensitizers in nonalcoholic fatty liver disease and steatohepatitis: Current steatus. Adv. Ther. 2009; 26 (10): 893–907.
  9. Li L., Yang G., L G., Tang Y., Li K. High-fat- and lipid-induced insulin resistance in rats: he comparison of glucose metabolism, plasma resistin and adiponectin levels. Ann Nutr. Metab. 2006; 50 (6): 499–505.
  10. Titov V.N. Toriya biologicheskih funkcij i ee primenenie pri vyyasnenii patogeneza rasprostranennyh zabolevanij cheloveka. Uspehi sovr. biol. 2008; 128 (5): 435-452.
  11. Roden M. How free fatty acids inhibit glucose utilization in human skeletal muscle. New. Physiol. Sci. 2004; 19: 92–96.
  12. Malone M., Evans J.J. Determining the relative amounts of positional isomers in complex mixtures of triglycerides using reversedphase high-performance liguid chromatography-tandem mass spectrometry. Lipids. 2004; 39 (3): 273–284.
  13. Bysted A., Helmer G., Lund P. Et al. Effect of dietary fatty acids on the postprandial fatty acid composition of triacylglycerol-rich lipoproteins in healthy male subjects. Eur. J. Clin. Nur. 2005; 59 (1): 24–34.
  14. Bracco U. Effect of triglyceride structure on fat absorption1-3 . Am. J. Clin. Nur. 1994; 60: 1002–1009.
  15. Malhi H., Goes G.J. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin. Liver. Dis. 2008 28 (4): 360–369.
  16. Oakes N.D., Furler S.M. Evaluation of free fatty acid metabolism in vivo. Ann. N.Y. Acad. Sci. 2002; 967: 158–175.
  17. Reid B.N., Ables G.P., Otlivanchik O.A. et al. Hepatic overexpresion o hormone-sensitive lipase and adipose triglyceride lipase promotes fatty acid oxidation, stimulates direct release of free fatty acids, and ameliorates steatosis. J. Biol. Chem. 2008; 283 (19): 13087–13099.
  18. Fragiskos B., Chan A.C., Choy P.C. Competition of n-3 and n-6 polyunsaturated fatty acids in the isolated perfused rat heart. Ann. Nutr. Metab. 1986; 30 (5): 331–334.
  19. Ivanov A.S. Osnovnye principy konformacionnogo raznoobraziya belkov dlya mediko-biologov. Biomed. himiya. 2011; 57 (1): 31-60.
  20. Bermudez B., Lopez S., Ortega A. et al. Oleic acid in olive oil: from a metabolic framework toward a clinical perspective. Curr. Pharm. Des. 2011; 17 (8): 831–843.
  21. Titov V.N. Ateroskleroz - problema obschej biologii: narushenie biologicheskih funkcij pitaniya i `endo`ekologii. Uspehi sovr. biol. 2009; 129 (2): 124-143.
  22. Berry S.E. Triacylglycerol structure and interesterificaton of palmitic and stearic acid-rich fats: an overview and implications for cardiovascular disease. Nutr. Res. Rev. 2009; 22 (1): 3–17.
  23. Tremblay A.J., Despres J.P., Riche M.E. et al. Associations between the fatty acid content of triglyceride, visceral adipose tissue accumulation, and components of he insulin resistance syndrome. Metabolism. 2004; 53 (3): 310–317.
  24. Rozhkova T.A., Amelyushkina V.A., Yarovaya E.B., Malyshev P.P., Titov V.N. Kliniko-laboratornoe vyyavlenie fenotipicheskih osobennostej u pacientov s vysokoj gipertrigliceridemiej. Klin. lab. diagnostika. 2011; 5: 10-16.
  25. Teng K.T., Nagapan G., Cheng H.M., Nesaretnam K. Palm olein ad olive oil cause a higher increase in postprandial lipemia compared with lard but had no effect on plasma glucose, insulin and adipocytokines. Lipids. 2011; 46 (4): 381–388.
  26. Sakurai M, Takamura T., Ota T. et al. Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease. J. Gastroenterol. 2007; 42 (4): 312–317.
  27. Huang Y., Fu J.F., Shi H.B., Liu L.R. Metabolism prevents nonalcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes. Zhonghua. Er. Ke. Za. Zhi. 2011; 49 (2): 139–145.
  28. Feldstein A.E., Lopez R., Tamimi T.A. et al. Mass spectrometric profiling of oxidized lipid products in human nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. J. Lipid. Esp. 2010; 51 (10): 3046–3054.
  29. Hal D., Poussin C., Velagapudi V.R. et al. Peroxisomal and microsomal lipid pathways associated with resistance to hepatic steatosis and reduced pro-inflammatory state. J. Biol. Chem. 2010; 285 (40): 31011–31023.
  30. Kuda O., Stankova B., Tvrzicka E. et al. prominent role of liver n elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet. J. Physiol. Pharmacol. 2009; 60 (4): 135–140.
  31. Fabbrini E., Magkos F., Su X. et al. Insulin sensitivity is not associated with palmitoleate availability in obese humans. J. Lipid. Res. 2011. 52 (4): 808–812.
  32. Hunter J.E. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids. 2001; 36 (7): 655–668.
  33. Macfarlane D.P., Zou X., Andrew R. et al. Metabolic pathways promoting intrahepatic fatty acid accumulation in methionine and choine deficiency: implications for he pathogenesis of steatohhepatits. Am. J. Physiol. Endocrinol. Metab. 2011; 300 (2): 402–409.
  34. Lim J.S., Mietus-Snyder M., Valente A. et al. The role of fructose in the pathogenesis of NAFLD an he metabolic syndrome. Nat. Rev. Gastroenterol. Hepatol. 2010; 7 (5): 251–264.
  35. Titov V.N. Insulin - gumoral’nyj faktor obespecheniya `energiej biologicheskoj funkcii lokomocii. Vestnik RAMN. 2005; 2: 3-8.
  36. Fessler M.B., Ruel L.L., Brown M. Tol-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr. Opin Lipidol. 2009; 20 (5): 379–385.
  37. Han M.S., Park S.Y., Shinzawa K. et al. Lysophosphatidylcholine as a death effector in he lipoapoptosis of hepatocytes. J. Lipid. Res. 2008; 49 (1): 84–97.
  38. Guthmann F., Haupt R., Looman A.C. et al. Fatty acid translocase/ CD36 mediaes the uptake of palmitate by type II pneumocytes. Am. Physiol. Soc. 1999; 277: 191–196.
  39. Momchilowa S., Tsuji K., Itabashi Y. et al. Resolution of triacylglycerol positional isomers by reversed-phase high-performance liguid chromatography. J. Sep. Sci. 2004; 27 (12): 1033–1036.
  40. Heath R.B., Karpe F., Milne R.W. et al. Selective portioning of dietary fatty acids into the VLDL TG pool In the early postprandial period. J. Lipid. Res. 2003; 44 (11): 2065–2072.
  41. Liu J., Jahn L.A., Fowler D.E. et al. Free fatty acids induce insulin resistance n both cardiac and skeletal muscle microvaculature in humans. J. Clin. Endocrinol. Metab. 2011; 96 (2): 438–446.
  42. Baajaj M., Suraamornkul S., Kashyap S., et al. Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels n subjects with strong family history of type 2 diabetes. J. Clin. Endocrinol. Metab. 2004; 89 (9): 4649–4655.
  43. Radesky J.S., Oken E., Rifas-Shiman S.L. et al. Diet during early pregnancy and development of gestational diabetes. Paediatr. Perinat. Epidemiol. 2008; 22 (10): 47–59.
  44. Lewis G.F., Steiner G. Acute effects of insulin in the control of VLDL production in humans. Implications for the insulin-resistant state. Diabetes. Care. 1996; 19 (4) 390–393.
  45. Woodward M., Tunstall-Pedoe H., Batty G.D. et al. The prognostic value of adipose tissue fatty acids for incident cardiovascular disease: results from 3944 subjects in the Scottish Heart Health Extended Cohort Study. Eur Heart. J. 2011; 32 (11): 1416–1423.
  46. Marinou K., Adiels M., Hodson L. et al. Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men. Br. J. Nutr. 2011; 105 (6): 857–865.
  47. Micallef M.A., Munro I.A., Gag M.L. An. Inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur. J. Clin. Nutr. 2009; 63 (9): 1154–1156.
  48. Kim-Dorner S.J., Deuster P.A. Zeno S.A. et al. Should triglycerides to high-density lipoprotein cholesterol ratio be used as surrogates for insulin resistance? Metabolism. 2010; 59 (2): 299–304.
  49. Berry S.E., Miller G.J., Sanders T.A. The solid fat content of stearic acid-rich fats determines their postprandial effects. Am. J. Clin. Nutr. 2007; 85 (6): 1486–1494.
  50. Paik M.J., Kim H., Lee J. et al. Separation of triacylglycerols and free fatty acids in microalgal lipids by solid-phase extraction for separate fatty acid profiling analysis by gas chromatography. J. Chromatogr. A. 2009; 1216 (31): 5917–5923.

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