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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2012; 58(1): 93-101

NF-kB activation as a molecular basis of pathological process by metabolic syndrome

Kaĭdashev IP.

    Higher State Educational Establishment of Ukraine“Ukrainian Medical Stomatological Academy”, Poltava, Ukraine


The paper examines the formation of evolutionary advanced causal factors set in modern conditions which may cause new pathological condition (state), being implemented through evo­lutionary fixed and standard pathological processes. The analysis of the notion of “metabolic syndrome” and its components has been performed. The correlation between insulin resistance, chronic inflammation, arterial hypertension, endothelial dysfunction and dyslipidemia has been indicated as the manifestations of one pathologic process, the central molecular basis of which is the activation of NF-kB. At the current stage it has been suggested to set up the conception of NF-kB permanent (long-lasting, low grade) activation as a possible model of pathological process.

Keywords: metabolic syndrome, insulin resistance, NF-kB.


  1. Alpern D.E. Pathological physiology. M.: Medicine, 1965 . 434 p.
  3. Bershtein L.M., Kovalenko I.G. "Metabolically healthy" obese individuals and metabolic signs of obesity in people with normal body weight: what is behind this? . Probl. endocrinology. 2010. N 3 P. 47-51. CrossRef  
  4. Zaichik A.Sh., Churilov L.P. Fundamentals of general pathology. Part 1. Fundamentals of general pathophysiology. SPb. : ELBY, 1999 .- 624 p.
  6. Izmaylova O.V., Shlikova O.A., Bobrova I.O., Kaydashev I.P. The sound of polymorphisms of genes TLR2 and TLR4 with the precedence of urogenital infections . Cytology and Genetics. 2011. No. 4. P.29-35.
  8. Pathological physiology . Ed. Corr. USSR Academy of Medical Sciences N.N. Zayko. K .: Vishcha school, 1985 .- 575 p.
  10. Abdul-Ghani M.A., Jenkinson C.P., Richardson D.K., Tripathy D., DeFronzo R.A. Insulin secretion and ac­tion in subjects with impaired fasting glucose and im­paired glucose tolerance: results from the Veterans Administration Genetic Epidemiology Study (VAGES) . Diabetes. 2006. 55. P. 1430-1435. CrossRef PubMed
  12. Alberti K., Zimmer P. Definition, diagnosis and classification of Diabetes mellitus and its complications, part1: diagnosis and classification of diabetes mellitus, provisional report of a World Health Organization consultation . Diabet. Med. 1998. 15. P. 539-553. CrossRef  
  13. Alberti K.G., Eckel R.H., Grundy S.M., Zimmet P.Z., Cleeman J.I., Donato K.A., Fruchart J.C., James W.P., Loria C.M., Smith S.C Harmonizing the metabolic syndrome: a joint interim statement of the Interna­tional Diabetes Federation Task Force on Epidemiol­ogy and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity . Circulation. 2009. 120. P. 1640-1645. CrossRef PubMed
  15. Alberti K.G., Zimmer P., Shaw J. IDF Epidemiology Task Force Consensus Group. The Metabolic Syn­drome a new worldwide definition . Lancet. 2005. 366. P. 1059-1062. CrossRef  
  16. Bajaj M., DeFronzo R.A. Metabolic and molecular basis of insulin resistance . J. Nucl. Cardiol. 2003. 10. P. 311-323. CrossRef  
  17. Bays H., Mandarino L., De Fronzo R.A. Role of the adipocytes, FFA, and ectopic fat in the pathogenesis of type 2 diabetes mellitus: PPAR agonists provide a rational therapeutic approach . J. Clin. Endocrinol. Metab. 2004. 89. P. 463-478. CrossRef PubMed
  19. Behrendt D., Ganz P. Endothelial function. From vascular biology to clinical applications . Amer. J. Cardiol. 2002. 21. P. 40L-48L.
  21. Coletta D.K., Balas B., Chavez A.O., Baig M., Abdul-Ghani M., Kashyap S.R., Folli F., Tripathy D., Mandarino L.J., Cornell J.E., Defronzo R.A., Jenkinson C.P. Effect of acute physiological hyperin-sulinemia on gene expression in human skeletal muscle in vivo . Amer. J. Physiol. Endocrinol. Metab. 2008. 294. P. E910-E917. CrossRef PubMed PubMedCentral
  23. De Alvaro C, Teruel T., Hernandez R., Lorenzo M. Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappa B kinase in a p38 mark-dependent manner . J. Biol. Chem. 2004. 279. P. 17070-17078. CrossRef PubMed
  25. De Fronzo R. A. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis : the missing links. The Claude Bernard lecture 2009 . Diabetologia. 2010. 53. P.1270-1287. CrossRef PubMed PubMedCentral
  27. Del Prato S., Leonetti F., Simonson D.C. Effect of sus­tained physiologic hyperinsulinaemia and hypergly-caemia on insulin secretion and insulin sensitivity in man . Ibid. 1994. 37. P. 1025-1035. CrossRef PubMed
  29. Folli F., Bouchie J.L., Kahn C.R., Hansen H., Feener E.P. Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels . J. Clin. Invest. 1997. 100. P. 2158-2169. CrossRef PubMed PubMedCentral
  31. Gao Z., Hwang D., Bataille F., Lefevre M., York D., Quon M.J., Ye J. Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex . J. Biol. Chem. 2002. 277. P. 48115-48121. CrossRef PubMed
  33. Garg R., Tripathy D., Dandona P. Insulin resistance as a proinflammatory state: mechanisms, mediators, and therapeutic interventions . Curr. Drug Targets. 2003. 4. P. 487-492. CrossRef PubMed
  35. Gerstein H.C., Miller M.E., Byington R.P., Goff D.C. Jr., Bigger J.T., Buse J.B., Cushman W.C., Genuth S., Ismail-Beigi F., Grimm R.H. Jr., Probsteld J.L., SimonsMorton D.G., Friedewald W.T. Effects of in­tensive glucosae lowering in type 2 diabetes . N. Engl. J. Med. 2008. 358. P. 2345-2359. CrossRef PubMed PubMedCentral
  37. Golovchenko I., Goalstone M.L., Watson P., Brownlee M., Draznin B. Hyperinsulinemia Enhances Transcrip­tional Activity of Nuclear Factor-kB Induced by An­giotensin II, Hyperglycemia, and Advanced Glyco­sylation End Products in Vascular Smooth Muscle Cells . Circulat. Res. 2000. 87. P. 746-762. CrossRef PubMed
  39. Grundy S. M., Cleeman J.I., Daniels S.R., Donato K.A., Eckel R.H., Franklin B.A., Gordon D.J., Krauss R.M., Savage P.J., Smith Jr. S.C., Spertus J.A., Costa F. Diagnosis and management of the metabolic syn­drome: An American Heart Association. National Heart, Lung, and Blood Institute Scientific Statement . Cir­culation. 2005. 112. P. 2735-2752. CrossRef PubMed
  41. Gulli G., Ferrannini E., Stern M., Haffner S., DeFronzo R.A. The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents . Diabetes. 1992. 41. P. 1575-1586. CrossRef PubMed
  43. Holman R.R., Thorne K.I., Farmer A.J., Davies M.J., Keenan J.F., Paul S., Levy J.C. Addition of Biphasic, Pran­dial, or Basal Insulin to Oral Therapy in Type 2 Diabetes . N. Engl. J. Med. 2007. 357. P. 1716-1730. CrossRef PubMed
  45. Kashyap S., Belfort R., Berria R., Suraamornkul S., Pratipranawatr T., Finlayson J., Barrentine A., Bajaj M., Mandarino L., DeFronzo R., Cusi K. Discordant effects of a chronic physiological increase in plasma FFA on insulin signaling in healthy subjects with or without a family history of type 2 diabetes . Amer. J. Physiol. Endocrinol. Metab. 2004. 287. P. E537-E546. CrossRef PubMed
  47. Kaydashev I.P., Rasin A.M., Shlykova O.A., Gorbas' I.M., Smirnova I.P., Petrushov A.V., Rasin M.S. Fre­quency of Pro12Ala-Polymorphism of the Gene PPARr2 in the Ukrainian Population and Its Possible Relation to the Development of the Metabolic Syndrome . Cytol. and Genet. 2007. 41, N 5. P.298-302. CrossRef  
  48. Miranda P.J., DeFronzo R.A., Califf R.M., Guyton J.R. Metabolic syndrome: evaluation of pathological and therapeutic outcomes . Amer. Heart J. 2005. 149. P. 20-45. CrossRef PubMed
  50. Naruse K., Shimizu K., Muramatsu M., Toki Y, Miyazaki Y, Okumura K., Hashimoto H., Ito T. Long-term inhibi­tion of NO synthesis promotes atherosclerosis in the hy-percholesterolemic rabbit thoracic aorta. PGH2 does not contribute to impaired endothelium-dependent relaxation . Arterioscler Thromb. 1994. 14. P. 746-752. CrossRef PubMed
  52. National Cholesterol Education Program (NCEP) Ex­pert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detec­tion, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report . Circulation. 2002. 106. P. 3143-3421. CrossRef PubMed
  54. Oeckinghaus A., Hayden M.S., Ghosh S. Crosstalk in NF-kB signaling pathway . Nat. Immunol. 2011. 12 (8). P. 695-708
  55. CrossRef PubMed  
  56. Patel A., MacMahon S., Chalmers J., Neal B., Billot L., Woodward M., Marre M., Cooper M., Glasziou P., Grobbee D.E., Hamet P., Harrap S., Heller S., Liu L.S., Mancia G. et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes . New Engl. J. Med. 2008. 358. P. 2560-2725.
  58. Reaven G. M. Banting Lecture 1988. Role of insulin resistance in human disease . Diabetes. 1988. 37. P. 1594-1607. CrossRef PubMed
  60. Unger R.H. Lipid overload and overflow: metabolic trauma and the metabolic sundrome . Trends Endocrinol. Metab. 2003. 14. P. 398-403. CrossRef PubMed

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