diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM2013449-51diaendo-6283Research ArticleДискуссияDiscussionСахарный диабет 2 типа: новые стороны патогенеза заболеванияNovel approach to pathophysiology of type 2 diabetes mellitusМахамеджановЭмиль КопеевичMukhamedzhanovEmil' Kopeevich

доктор медицинских наук, профессор, главный научный сотрудник лаборатории фармакологии и токсикологии

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

labpharma@mail.ruЕсыревОлег ВиктововичEsyrevOleg Viktorovich

доктор биологических наук, профессор, главный научный сотрудник лаборатории фармакологии и токсикологии

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

labpharma@mail.ruРГП Научный центр противоинфекционных препаратов, АлматыКазахстанAnti-infective Drugs Research Centre, AlmatyKazakhstan2013181220131644951Copyright © Махамеджанов Э.К., Есырев О.В., 20132013Махамеджанов Э.К., Есырев О.В.Mukhamedzhanov E.K., Esyrev O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/6283

Представлена модель взаимосвязи между обменом белков, жиров и углеводов в зависимости от путей транспорта углеродного скелета и процессов образования и утилизации энергии. Модель позволяет понять роль белкового обмена в нарушении толерантности к глюкозе в абсорбтивный период. Обсуждается значение цитокинов в регуляции энергетического гомеостаза на уровне mTOR (mammalian target of rapamycin) ? ключевого звена инсулинового каскада, рассматриваются причины развития инсулинорезистентности.

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.

сахарный диабет 2 типапатогенезбелковый обменцитокиныинсулинорезистентностьtype 2 diabetes mellituspathogenesisprotein metabolismcytokinesinsulin resistanceReferencesNurdlie RC. Fine tuning of glucose concentrations. Trends in Biochemical Sciences. 1985; 10(2): 70–75.Nurdlie RC. Fine tuning of glucose concentrations. Trends in Biochemical Sciences. 1985; 10(2): 70–75.DOI: 10.1016/0968-0004(85)90236-1DOI: 10.1016/0968-0004(85)90236-1Северин ЕС, Алейникова ТЛ, Осипов ЕВ. Биохимия. М: Медицина; 2000. 164 с. [Severin ES, Aleynikova TL, Osipov EV. Biokhimiya. Moscow: Meditsina; 2000. 164 p.]Северин ЕС, Алейникова ТЛ, Осипов ЕВ. Биохимия. М: Медицина; 2000. 164 с. [Severin ES, Aleynikova TL, Osipov EV. Biokhimiya. Moscow: Meditsina; 2000. 164 p.]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.]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.]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.]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.]Rabinowits D, Zierler KI. Forearm metabolism in obesity and its response to intraarterial insulin. The Journal of Clinical Investigation. 1962;41(12):2173–2181.Rabinowits D, Zierler KI. Forearm metabolism in obesity and its response to intraarterial insulin. The Journal of Clinical Investigation. 1962;41(12):2173–2181.DOI: 10.1172/JCI104676DOI: 10.1172/JCI104676Wise 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.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.DOI: 10.1056/NEJM197303082881003DOI: 10.1056/NEJM197303082881003Linn 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.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.DOI: 10.1210/jc.81.11.3938DOI: 10.1210/jc.81.11.3938Kalogeropoulou 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.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.DOI: 10.1016/j.metabol.2008.09.001DOI: 10.1016/j.metabol.2008.09.001Halton 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.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.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.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.DOI: 10.1172/JCI1326DOI: 10.1172/JCI1326Hinault 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.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.DOI: 10.1096/fj.03-1409fjeDOI: 10.1096/fj.03-1409fjeMacotela 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).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).DOI: 10.1371/journal.pone.0021187DOI: 10.1371/journal.pone.0021187Layman DK. The Role of Leucine in Weight Loss Diets and Glucose Homeostasis. The Journal of Nutrition. 2003;133(1):261S–267S.Layman DK. The Role of Leucine in Weight Loss Diets and Glucose Homeostasis. The Journal of Nutrition. 2003;133(1):261S–267S.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.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.DOI: 10.1074/jbc.274.17.11647DOI: 10.1074/jbc.274.17.11647Lynch 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.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.DOI: 10.1002/(SICI)1097-4644(20000501)77:2<234::AID-JCB7>3.0.CO;2-IDOI: 10.1002/(SICI)1097-4644(20000501)77:2<234::AID-JCB7>3.0.CO;2-IAdeva 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.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.DOI: 10.1007/s00726-011-1088-7DOI: 10.1007/s00726-011-1088-7Bastard 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.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.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.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.DOI: 10.1111/j.1748-1708.2010.02151.xDOI: 10.1111/j.1748-1708.2010.02151.xBolster 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.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.DOI: 10.1113/jphysiol.2003.047019DOI: 10.1113/jphysiol.2003.047019

The authors declare that there are no conflicts of interest present.