From metabolism to pathology: тhe role of sodium-glucose cotransporter-1 in the pathogenesis of type 2 diabetes mellitus
https://doi.org/10.62751/2713-0177-2024-5-3-07
Abstract
Type 2 diabetes mellitus (DM2) is one of the most common metabolic diseases of our time, affecting millions of people around the world. In recent years, the attention of researchers has been attracted by type 1 sodium-glucose cotransporter inhibitors (NGL-1), which open up new horizons in the treatment of this disease. Currently, there is data on the location of NGL-1 in many organs and tissues. Excessive activity of these transporters may contribute to an increase in blood glucose levels, which makes inhibition of this cotransporter a promising approach for glycemia management. This article will consider the effects of inhibition of iSGLT-1, their effect on the pathogenesis of DM2, and will also present the results of clinical studies confirming the effectiveness and safety of inhibition of iSGLT-1 in patients with DM2.
About the Authors
T. Yu. Demidova
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Tatiana Yu. Demidova – D. Sci. (Med.), Prof.
Moscow
A. S. Teplova
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Anna S. Teplova – assistant at the Department of endocrinology
Moscow
E. V. Stepanova
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Ekaterina V. Stepanova – student
Moscow
D. S. Amirian
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Diana S. Amiryan – student
Moscow
References
1. Недосугова Л.В. Роль эндокринной системы в поддержании гомеостаза глюкозы в норме и при патологии. РМЖ. Медицинское обозрение. 2021; 5(9): 586–591. doi: 10.32364/2587-6821-2021-5-9-586-591.
2. Sano R, Shinozaki Y, Ohta T. Sodium-glucose cotransporters: Functional properties and pharmaceutical potential. J Diabetes Investig. 2020; 11(4): 770–82. doi: 10.1111/jdi.13255.
3. Vrhovac I, Balen Eror D, Klessen D et al Localizations of Na(+)‐D‐glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Arch. 2015; 467(9): 1881–98. doi: 10.1007/s00424-014-1619-7.
4. Шестакова М.В., Аметов А.С., Анциферов М.Б. с соавт. Канаглифлозин: от гликемического контроля до улучшения сердечно-сосудистого и почечного прогноза у пациентов с сахарным диабетом 2 типа. Резолюция совета экспертов. Сахарный диабет. 2021; 24(5): 479–486. doi: 10.14341/DM12848.
5. Цыганкова О.В., Веретюк В.В., Аметов А.С. Инкретины сегодня: множественные эффекты и терапевтический потенциал. Сахарный диабет. 2019; 22(1): 70–78. doi: 10.14341/DM9841.
6. Juris J. Meier. Роль терапии на основе инкретинов в лечении сахарного диабета 2 типа: прошлое, настоящее и будущее. Сахарный диабет. 2019; 22(5): 461–466. doi: 10.14341/DM11493.
7. Малолеткина Е.С., Фадеев В.В. Преимущества ингибирования натрий-глюкозного котранспортера 1 типа в повседневной клинической практике. РМЖ. 2022; (1): 20–25.
8. Polidori D, Sha S, Mudaliar S et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: Results of a randomized, placebo-controlled study. Diabetes Care. 2013; 36(8): 2154–61. doi: 10.2337/dc12-2391.
9. Ghezzi C, Loo DDF, Wright EM. Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia. 2018; 61(10): 2087–97. doi: 10.1007/s00125-018-4656-5.
10. Wilding J. The role of the kidneys in glucose homeostasis in type 2 diabetes: Clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors. Metabolism. 2014; 63(10): 1228–37. doi: 10.1016/j.metabol.2014.06.018.
11. Покровская Е.В., Трубицына Н.П., Зайцева Н.В. Нефропротективные свойства сахароснижающих препаратов. ConsiliumMedicum. 2019; 21(4): 35–39. doi: 10.26442/20751753.2019.4.190332.
12. Kondo H, Akoumianakis I, Badi I et al. Effects of canagliflozin on human myocardial redox signalling: Clinical implications. Eur Heart J. 2021; 42(48): 4947–60. doi: 10.1093/eurheartj/ehab420.
13. Lambert R, Srodulski S, Peng X et al. Intracellular Na+ concentration ([Na+]i) is elevated in diabetic hearts due to enhanced Na+-glucose cotransport. J Am Heart Assoc. 2015; 4(9): e002183. doi: 10.1161/JAHA.115.002183.
14. Kohlhaas M, Liu T, Knopp A et al. Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes. Circulation. 2010; 121(14): 1606–13. doi: 10.1161/CIRCULATIONAHA.109.914911.
15. Koepsell H. Glucose transporters in brain in health and disease. Pflugers Arch. 2020; 472(9): 1299–343. doi: 10.1007/s00424-020-02441-x.
16. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011; 91(2): 733–94. doi: 10.1152/physrev.00055.2009.
17. Garnett JP, Baker EH, Baines DL. Sweet talk: Insights into the nature and importance of glucose transport in lung epithelium. Eur Respir J. 2012; 40(5): 1269–76. doi: 10.1183/09031936.00052612.
18. Pezzulo AA, Gutierrez J, Duschner KS et al. Glucose depletion in the airway surface liquid is essential for sterility of the airways. PLoS One. 2011; 6(1): e16166. doi: 10.1371/journal.pone.0016166.
19. Tamer A., Karabay O., Ekerbicer H. Staphylococcus aureus nasal carriage and associated factors in type 2 diabetic patients. Jpn J Infect. Dis. 2006; 59 (1): 10–14.
20. Zhang QR, Chen H, Liu B, Zhou M. Methicillin-resistant Staphylococcus aureus pneumonia in diabetics: A single-center, retrospective analysis. Chin Med J (Engl). 2019; 132(12): 1429–34. doi: 10.1097/CM9.0000000000000270.
21. Balen D, Ljubojevic M, Breljak D et al. Revised immunolocalization of the Na+-D-glucose cotransporter SGLT1 in rat organs with an improved antibody. Am J Physiol Cell Physiol. 2008; 295(2): C475–89. doi: 10.1152/ajpcell.00180.2008.
22. Masyuk AI, Masyuk TV, Tietz PS et al. Intrahepatic bile ducts transport water in response to absorbed glucose. Am J Physiol Cell Physiol. 2002; 283(3): C785–91. doi: 10.1152/ajpcell.00118.2002.
23. Liang X, Hou X, Bouhamdan M et al. Sotagliflozin attenuates liver-associated disorders in cystic fibrosis rabbits. JCI Insight. 2024; 9(6): e165826. doi: 10.1172/jci.insight.165826.
24. Suga T, Kikuchi O, Kobayashi M et al. SGLT1 in pancreatic α cells regulates glucagon secretion in mice, possibly explaining the distinct effects of SGLT2 inhibitors on plasma glucagon levels. Mol Metab. 2019; 19: 1–12. doi: 10.1016/j.molmet.2018.10.009.
25. Porth R, Oelerich K, Sivanandy MS. The role of sodium-glucose cotransporter-2 inhibitors in the treatment of polycystic ovary syndrome: A review. J Clin Med. 2024; 13(4): 1056. doi: 10.3390/jcm13041056.
26. Scafoglio С, Hirayama BA, Kepe V et al. Functional expression of sodium-glucose transporters in cancer. Proc Natl Acad Sci USA. 2015; 11 (30): E4111–19. doi: 10.1073/pnas.1511698112.
27. Ota T, Ishikawa T, Sakakida T et al. Treatment with broad-spectrum antibiotics upregulates Sglt1 and induces small intestinal villous hyperplasia in mice. J Clin Biochem Nutr. 2022; 70(1): 21–27. doi: 10.3164/jcbn.21-42.
28. Ho HJ, Kikuchi K, Oikawa D et al. SGLT-1-specific inhibition ameliorates renal failure and alters the gut microbial community in mice with adenine-induced renal failure. PhysiolRep. 2021; 9(24): e15092. doi: 10.14814/phy2.15092.
29. Bauer PV, Duca FA, Waise TMZ et al. Metformin alters upper small intestinal microbiota that impact a glucose-sglt1-sensing glucoregulatory pathway. Cell Metab. 2018; 27(1): 101–117.e5. doi: 10.1016/j.cmet.2017.09.019.
30. Zubiaga L, Briand O, Auger F et al. Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes. Science. 2023; 26(4): 106057. doi: 10.1016/j.isci.2023.106057.
Supplementary files
Review
For citations:
Demidova T.Yu., Teplova A.S., Stepanova E.V., Amirian D.S. From metabolism to pathology: тhe role of sodium-glucose cotransporter-1 in the pathogenesis of type 2 diabetes mellitus. FOCUS. Endocrinology. 2024;5(3):55-63. (In Russ.) https://doi.org/10.62751/2713-0177-2024-5-3-07
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