Novel approach to pathophysiology of type 2 diabetes mellitus

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In this paper, we present a model of interplay between protein, lipid and carbohydrate metabolic pathways with regard to the carbon chain transporting systems, as well as generation and consumption of energy. This model elucidates the role of protein metabolism in the impairment of glucose tolerance during the absorption period. We also discuss the effects on energy homeostasis exercised by cytokines via mTOR pathway (the key factor of insulin signalling) considering the phenomenon of insulin resistance.

About the authors

Emil' Kopeevich Mukhamedzhanov

Anti-infective Drugs Research Centre, Almaty

Author for correspondence.

Kazakhstan MD, PhD, Professor, Chief Researcher in the Pharmacology and toxycology laboratory

Oleg Viktorovich Esyrev

Anti-infective Drugs Research Centre, Almaty


Kazakhstan PhD, Professor, Chief Researcher in the Pharmacology and toxycology laboratory


  1. Nurdlie RC. Fine tuning of glucose concentrations. Trends in Biochemical Sciences. 1985; 10(2): 70–75.
  2. doi: 10.1016/0968-0004(85)90236-1
  3. Северин ЕС, Алейникова ТЛ, Осипов ЕВ. Биохимия. М: Медицина; 2000. 164 с. [Severin ES, Aleynikova TL, Osipov EV. Biokhimiya. Moscow: Meditsina; 2000. 164 p.]
  4. Марра Р, Греннер Д, Мейес П, Родуэлл В. Биохимия человека. Том 1. М: Мир; 1993. 381 с. [Marra R, Grenner D, Meyes P, Roduell V. Biokhimiya cheloveka. Vol 1. Moscow: Mir; 1993. 381 p.]
  5. Мухамеджанов ЭК. Взаимосвязь между обменом нутриентов на уровне аланинового цикла в зависимости от действия факторов окружающей среды. Автореферат диссертации д.м.н. по специальности 03.00.04 – биологическая химия. Алма-Ата; 1990. 42 с. [Mukhamedzhanov EK. Vzaimosvyaz' mezhdu obmenom nutrientov na urovne alaninovogo tsikla v zavisimosti ot deystviya faktorov okruzhayushchey sredy [Dissertation]. Alma-Ata; 1990.]
  6. Rabinowits D, Zierler KI. Forearm metabolism in obesity and its response to intraarterial insulin. The Journal of Clinical Investigation. 1962;41(12):2173–2181.
  7. doi: 10.1172/JCI104676
  8. Wise JK, Hendler R, Felig P. Evaluation of Alpha-Cell Function by Infusion of Alanine in Normal, Diabetic and Obese Subjects. New England Journal of Medicine. 1973;288(10):487–490.
  9. doi: 10.1056/NEJM197303082881003
  10. Linn T, Geyer R, Prassek S, Laube H. Effect of dietary protein intake on insulin secretion and glucose metabolism in insulin-dependent diabetes mellitus. Journal of Clinical Endocrinology and Metabolism. 1996;81(11):3938–3943.
  11. doi: 10.1210/jc.81.11.3938
  12. Kalogeropoulou D, LaFave L, Schweim K, Gannon MC, Nuttall FQ. Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose. Metabolism: Clinical and Experimental. 2008;57(12):1747-1752.
  13. doi: 10.1016/j.metabol.2008.09.001
  14. Halton TL, Hu FB. The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr. 2004;23: 373–385.
  15. Patti ME, Brambilla E, Luzi L, Landaker EJ, Kahn CR. Bidirectional modulation of insulin action by amino acids. J Clin Invest 1998;101(7):1519–1529.
  16. doi: 10.1172/JCI1326
  17. Hinault C, Mothe-Satney I, Gautier N, Lawrence JC, Van_Obberghen E. Amino acids and leucine allow insulin activation of the PKB/mTOR pathway in normal adipocytes treated with wortmannin and in adipocytes from db/db mice. FASEB J. 2004.18.1894–1896 2004 Oct;18(15):1894–1896.
  18. doi: 10.1096/fj.03-1409fje
  19. Macotela Y, Emanuelli B, Bång AM, Espinoza DO, Boucher J, Beebe K, et al. Dietary leucine an environmental modifier of insulin resistance acting on multiple levels of metabolism. PLoS One 2011;6(6).
  20. doi: 10.1371/journal.pone.0021187
  21. Layman DK. The Role of Leucine in Weight Loss Diets and Glucose Homeostasis. The Journal of Nutrition. 2003;133(1):261S–267S.
  22. Kimball SR, Shantz LM, Horetsky RL, Jefferson LS. Leucine Regulates Translation of Specific mRNAs in L6 Myoblasts through mTOR-mediated Changes in Availability of eIF4E and Phosphorylation of Ribosomal Protein S6. Journal of Biological Chemistry. 1999;274(17):11647–11652.
  23. doi: 10.1074/jbc.274.17.11647
  24. Lynch CJ, Fox HL, Vary TC, Jefferson LS, Kimball SR. Regulation of amino acid–sensitive TOR signaling by leucine analogues in adipocytes. Journal of Cellular Biochemistry. 2000;77(2):234–251.
  25. doi: 10.1002/(SICI)1097-4644(20000501)77:2<234::AID-JCB7>3.0.CO;2-I
  26. Adeva M, Calviño J, Souto G, Donapetry C. Insulin resistance and the metabolism of branched-chain amino acids in humans. Amino Acids. 2012;43(1):171–181.
  27. doi: 10.1007/s00726-011-1088-7
  28. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur. Cytokine Netw 2006;17(17):4–12.
  29. Apró W, Blomstrand E. Influence of supplementation with branched-chain amino acids in combination with resistance exercise on p70S6 kinase phosphorylation in resting and exercising human skeletal muscle. Acta Physiol (Oxf) 2010;200(3):237–248.
  30. doi: 10.1111/j.1748-1708.2010.02151.x
  31. Bolster DR, Kubica N, Crozier SJ, Williamson DL, Farrell PA, Kimball SR, et al. Immediate response of mammalian target of rapamycin (mTOR)-mediated signalling following acute resistance exercise in rat skeletal muscle. J Physiol 2003 Aug;553(Pt 1):213–220.
  32. doi: 10.1113/jphysiol.2003.047019

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Copyright (c) 2013 Mukhamedzhanov E.K., Esyrev O.V.

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