Skip to content
2000
image of Interlinking the Cross Talk on Branched Chain Amino Acids, Water Soluble Vitamins and Adipokines in the Type 2 Diabetes Mellitus Etiology

Abstract

Type 2 Diabetes Mellitus (T2DM) is an etiologically diverse metabolic dysfunction that, if untreated, leads to chronic hyperglycemia. Understanding the etiology of T2DM is critical, as it represents one of the most formidable medical challenges of the twenty-first century. Traditionally, insulin resistance has been recognized as the primary risk factor and a well-known consequence of type 2 diabetes. Emerging evidence suggests that branched-chain amino acids (BCAAs), adipokines, and deficiencies in water-soluble vitamins, such as thiamine and pyridoxine, play significant roles in the development of insulin resistance, a key feature of T2DM. These factors are interconnected through the AMP-activated protein kinase (AMPK) pathway, which regulates various metabolic processes, including glucose transport, lipid synthesis, and inflammatory responses. Dysregulation of AMPK is linked to insulin resistance and metabolic syndrome-related illnesses. Understanding the interplay between BCAAs, adipokines, vitamins, and AMPK may offer new therapeutic targets for the prevention and treatment of diabetes mellitus.

© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode.
Loading

Article metrics loading...

/content/journals/emiddt/10.2174/0118715303305579241014112730
2025-01-08
2025-05-13
The full text of this item is not currently available.

References

  1. Classification of diabetes mellitus. World Health Organization Website. https://apps.who.int/iris/rest/bitstreams/1233344/retrieve 2019.
  2. The top 10 causes of death. World Health Organization. http://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death 2020.
  3. Ding C. Egli L. Bosco N. Sun L. Goh H.J. Yeo K.K. Yap J.J.L. Actis-Goretta L. Leow M.K.S. Magkos F. Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults. Front. Nutr. 2021 8 664939 10.3389/fnut.2021.664939 33996878
    [Google Scholar]
  4. Yao H. Li K. Wei J. Lin Y. Liu Y. The contradictory role of branched-chain amino acids in lifespan and insulin resistance. Front. Nutr. 2023 10 1189982 10.3389/fnut.2023.1189982 37408986
    [Google Scholar]
  5. Tanase D.M. Gosav E.M. Botoc T. Floria M. Tarniceriu C.C. Maranduca M.A. Haisan A. Cucu A.I. Rezus C. Costea C.F. Depiction of Branched-Chain Amino Acids (BCAAs) in Diabetes with a Focus on Diabetic Microvascular Complications. J. Clin. Med. 2023 12 18 6053 10.3390/jcm12186053 37762992
    [Google Scholar]
  6. Hernandez N. Lokhnygina Y. Ramaker M.E. Ilkayeva O. Muehlbauer M.J. Crawford M.L. Grant R.P. Hsia D.S. Jain N. Bain J.R. Armstrong S. Newgard C.B. Freemark M. Gumus Balikcioglu P. Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes. J. Clin. Endocrinol. Metab. 2024 109 4 e1345 e1358 10.1210/clinem/dgad708 38066593
    [Google Scholar]
  7. Cuomo P. Capparelli R. Iannelli A. Iannelli D. Role of Branched-Chain Amino Acid Metabolism in Type 2 Diabetes, Obesity, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease. Int. J. Mol. Sci. 2022 23 8 4325 10.3390/ijms23084325 35457142
    [Google Scholar]
  8. Ziegler D. Reiners K. Strom A. Obeid R. Association between diabetes and thiamine status - A systematic review and meta-analysis. Metabolism 2023 144 155565 10.1016/j.metabol.2023.155565 37094704
    [Google Scholar]
  9. Muley A. Fernandez R. Green H. Muley P. Effect of thiamine supplementation on glycaemic outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. BMJ Open 2022 12 8 e059834 10.1136/bmjopen‑2021‑059834 36008064
    [Google Scholar]
  10. Rad M.G. Sharifi M. Meamar R. Soltani N. The role of pancreas to improve hyperglycemia in STZ-induced diabetic rats by thiamine disulfide. Nutr. Diabetes 2022 12 1 32 10.1038/s41387‑022‑00211‑5 35725834
    [Google Scholar]
  11. Francisco V. Pino J. Gonzalez-Gay M.A. Mera A. Lago F. Gómez R. Mobasheri A. Gualillo O. Adipokines and inflammation: is it a question of weight? Br. J. Pharmacol. 2018 175 10 1569 1579 10.1111/bph.14181 29486050
    [Google Scholar]
  12. Kang Y.E. Kim J.M. Joung K.H. Lee J.H. You B.R. Choi M.J. Ryu M.J. Ko Y.B. Lee M.A. Lee J. Ku B.J. Shong M. Lee K.H. Kim H.J. The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction. PLoS One 2016 11 4 e0154003 10.1371/journal.pone.0154003 27101398
    [Google Scholar]
  13. Jaganathan R. Ravindran R. Dhanasekaran S. Emerging Role of Adipocytokines in Type 2 Diabetes as Mediators of Insulin Resistance and Cardiovascular Disease. Can. J. Diabetes 2018 42 4 446 456.e1 10.1016/j.jcjd.2017.10.040 29229313
    [Google Scholar]
  14. Melnik B.C. Leucine signaling in the pathogenesis of type 2 diabetes and obesity. World J. Diabetes 2012 3 3 38 53 10.4239/wjd.v3.i3.38 22442749
    [Google Scholar]
  15. Layman D.K. The role of leucine in weight loss diets and glucose homeostasis. J. Nutr. 2003 133 1 261S 267S 10.1093/jn/133.1.261S 12514305
    [Google Scholar]
  16. Wild S. Roglic G. Green A. Sicree R. King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004 27 5 1047 1053 10.2337/diacare.27.5.1047 15111519
    [Google Scholar]
  17. Wang T.J. Larson M.G. Vasan R.S. Cheng S. Rhee E.P. McCabe E. Lewis G.D. Fox C.S. Jacques P.F. Fernandez C. O’Donnell C.J. Carr S.A. Mootha V.K. Florez J.C. Souza A. Melander O. Clish C.B. Gerszten R.E. Metabolite profiles and the risk of developing diabetes. Nat. Med. 2011 17 4 448 453 10.1038/nm.2307 21423183
    [Google Scholar]
  18. Floegel A. Stefan N. Yu Z. Mühlenbruch K. Drogan D. Joost H.G. Fritsche A. Häring H.U. Hrabě de Angelis M. Peters A. Roden M. Prehn C. Wang-Sattler R. Illig T. Schulze M.B. Adamski J. Boeing H. Pischon T. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 2013 62 2 639 648 10.2337/db12‑0495 23043162
    [Google Scholar]
  19. Zhao X. Han Q. Liu Y. Sun C. Gang X. Wang G. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review. J. Diabetes Res. 2016 2016 1 12 10.1155/2016/2794591 27642608
    [Google Scholar]
  20. Chen T. Ni Y. Ma X. Bao Y. Liu J. Huang F. Hu C. Xie G. Zhao A. Jia W. Jia W. Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations. Sci. Rep. 2016 6 1 20594 10.1038/srep20594 26846565
    [Google Scholar]
  21. Würtz P. Mäkinen V.P. Soininen P. Kangas A.J. Tukiainen T. Kettunen J. Savolainen M.J. Tammelin T. Viikari J.S. Rönnemaa T. Kähönen M. Lehtimäki T. Ripatti S. Raitakari O.T. Järvelin M.R. Ala-Korpela M. Metabolic signatures of insulin resistance in 7,098 young adults. Diabetes 2012 61 6 1372 1380 10.2337/db11‑1355 22511205
    [Google Scholar]
  22. Lee C.C. Watkins S.M. Lorenzo C. Wagenknecht L.E. Il’yasova D. Chen Y.D.I. Haffner S.M. Hanley A.J. Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 2016 39 4 582 588 10.2337/dc15‑2284 26895884
    [Google Scholar]
  23. Yamada C. Kondo M. Kishimoto N. Shibata T. Nagai Y. Imanishi T. Oroguchi T. Ishii N. Nishizaki Y. Association between insulin resistance and plasma amino acid profile in non-diabetic J apanese subjects. J. Diabetes Investig. 2015 6 4 408 415 10.1111/jdi.12323 26221519
    [Google Scholar]
  24. Tillin T. Hughes A.D. Wang Q. Würtz P. Ala-Korpela M. Sattar N. Forouhi N.G. Godsland I.F. Eastwood S.V. McKeigue P.M. Chaturvedi N. Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall And Brent REvisited) Study. Diabetologia 2015 58 5 968 979 10.1007/s00125‑015‑3517‑8 25693751
    [Google Scholar]
  25. Tai E.S. Tan M.L.S. Stevens R.D. Low Y.L. Muehlbauer M.J. Goh D.L.M. Ilkayeva O.R. Wenner B.R. Bain J.R. Lee J.J.M. Lim S.C. Khoo C.M. Shah S.H. Newgard C.B. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia 2010 53 4 757 767 10.1007/s00125‑009‑1637‑8 20076942
    [Google Scholar]
  26. Felig P. Marliss E. Cahill G.F. Jr Plasma amino acid levels and insulin secretion in obesity. N. Engl. J. Med. 1969 281 15 811 816 10.1056/NEJM196910092811503 5809519
    [Google Scholar]
  27. Newgard C.B. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab. 2012 15 5 606 614 10.1016/j.cmet.2012.01.024 22560213
    [Google Scholar]
  28. Lynch C.J. Adams S.H. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat. Rev. Endocrinol. 2014 10 12 723 736 10.1038/nrendo.2014.171 25287287
    [Google Scholar]
  29. Saltiel A.R. Kahn C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001 414 6865 799 806 10.1038/414799a 11742412
    [Google Scholar]
  30. Roberson P.A. Jefferson L.S. Kimball S.R. Convergence of signaling pathways in mediating actions of leucine and IGF-1 on mTORC1 in L6 myoblasts. Am. J. Physiol. Cell Physiol. 2022 323 3 C804 C812 10.1152/ajpcell.00183.2022 35912992
    [Google Scholar]
  31. Liu H. Liu R. Xiong Y. Li X. Wang X. Ma Y. Guo H. Hao L. Yao P. Liu L. Wang D. Yang X. Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: involving mTORC1 and mTORC2. Amino Acids 2014 46 8 1971 1979 10.1007/s00726‑014‑1752‑9 24806638
    [Google Scholar]
  32. Li X. Wang X. Liu R. Ma Y. Guo H. Hao L. Yao P. Liu L. Sun X. He K. Cao W. Yang X. Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin‐target tissues. Mol. Nutr. Food Res. 2013 57 6 1067 1079 10.1002/mnfr.201200311 23404947
    [Google Scholar]
  33. Balage M. Dupont J. Mothe-Satney I. Tesseraud S. Mosoni L. Dardevet D. Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance. J. Nutr. Biochem. 2011 22 3 219 226 10.1016/j.jnutbio.2010.02.001 20558053
    [Google Scholar]
  34. Zhang Y. Guo K. LeBlanc R.E. Loh D. Schwartz G.J. Yu Y.H. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes 2007 56 6 1647 1654 10.2337/db07‑0123 17360978
    [Google Scholar]
  35. Bernard J.R. Liao Y.H. Hara D. Ding Z. Chen C.Y. Nelson J.L. Ivy J.L. An amino acid mixture improves glucose tolerance and insulin signaling in Sprague-Dawley rats. Am. J. Physiol. Endocrinol. Metab. 2011 300 4 E752 E760 10.1152/ajpendo.00643.2010 21304065
    [Google Scholar]
  36. Saha A.K. Xu X.J. Lawson E. Deoliveira R. Brandon A.E. Kraegen E.W. Ruderman N.B. Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes 2010 59 10 2426 2434 10.2337/db09‑1870 20682696
    [Google Scholar]
  37. Xiao F. Huang Z. Li H. Yu J. Wang C. Chen S. Meng Q. Cheng Y. Gao X. Li J. Liu Y. Guo F. Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes 2011 60 3 746 756 10.2337/db10‑1246 21282364
    [Google Scholar]
  38. Neinast M. Murashige D. Arany Z. Branched Chain Amino Acids. Annu. Rev. Physiol. 2019 81 1 139 164 10.1146/annurev‑physiol‑020518‑114455 30485760
    [Google Scholar]
  39. Kumar M.A. Bitla A.R. Raju K.V. Manohar S.M. Kumar V.S. Narasimha S.R. Branched chain amino acid profile in early chronic kidney disease. Saudi J. Kidney Dis. Transpl. 2012 23 6 1202 1207 10.4103/1319‑2442.103560 23168849
    [Google Scholar]
  40. Wiley K.D. Gupta M. Vitamin B1 (Thiamine) Deficiency. StatPearls Treasure Island (FL): StatPearls Publishing 2024
    [Google Scholar]
  41. Beltramo E. Berrone E. Tarallo S. Porta M. Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol. 2008 45 3 131 141 10.1007/s00592‑008‑0042‑y 18581039
    [Google Scholar]
  42. Beltramo E. Mazzeo A. Porta M. Thiamine and diabetes: back to the future? Acta Diabetol. 2021 58 11 1433 1439 10.1007/s00592‑021‑01752‑4 34091762
    [Google Scholar]
  43. Anwar A. Ahmed Azmi M. Siddiqui J.A. Panhwar G. Shaikh F. Ariff M. Thiamine level in type I and type II diabetes mellitus patients: a comparative study focusing on hematological and biochemical evaluations. Cureus 2020 12 5 e8027 10.7759/cureus.8027 32528766
    [Google Scholar]
  44. Karachalias N. Babaei-Jadidi R. Kupich C. Ahmed N. Thornalley P.J. High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats. Ann. N. Y. Acad. Sci. 2005 1043 1 777 783 10.1196/annals.1333.090 16037305
    [Google Scholar]
  45. Waheed P. Naveed A.K. Ahmed T. Thiamine deficiency and its correlation with dyslipidaemia in diabetics with microalbuminuria. J. Pak. Med. Assoc. 2013 63 3 340 345 23914634
    [Google Scholar]
  46. Al-Attas O.S. Al-Daghri N.M. Alfadda A.A. Abd-Alrahman S.H. Sabico S. Blood thiamine and its phosphate esters as measured by high-performance liquid chromatography: levels and associations in diabetes mellitus patients with varying degrees of microalbuminuria. J. Endocrinol. Invest. 2012 35 11 951 956 10.3275/8126 22107884
    [Google Scholar]
  47. Kaimoto T. Shibuya M. Nishikawa K. Maeda H. High incidence of lipid deposition in the liver of rats fed a diet supplemented with branched-chain amino acids under vitamin B6 deficiency. J. Nutr. Sci. Vitaminol. (Tokyo) 2013 59 1 73 78 10.3177/jnsv.59.73 23535543
    [Google Scholar]
  48. Liu Z. Li P. Zhao Z.H. Zhang Y. Ma Z.M. Wang S.X. Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation in Apoe−/− mice fed with high-fat diet. J. Diabetes Res. 2016 2016 1 8 10.1155/2016/1748065 26881239
    [Google Scholar]
  49. Unoki-Kubota H. Yamagishi S. Takeuchi M. Bujo H. Saito Y. Pyridoxamine, an inhibitor of advanced glycation end product (AGE) formation ameliorates insulin resistance in obese, type 2 diabetic mice. Protein Pept. Lett. 2010 17 9 1177 1181 10.2174/092986610791760423 20441560
    [Google Scholar]
  50. Zemel M.B. Bruckbauer A. Effects of a leucine and pyridoxine-containing nutraceutical on fat oxidation, and oxidative and inflammatory stress in overweight and obese subjects. Nutrients 2012 4 6 529 541 10.3390/nu4060529 22822451
    [Google Scholar]
  51. Abraham P.M. Kuruvilla K.P. Mathew J. Malat A. Joy S. Paulose C.S. Alterations in hippocampal serotonergic and INSR function in streptozotocin induced diabetic rats exposed to stress: neuroprotective role of pyridoxine and Aegle marmelose. J. Biomed. Sci. 2010 17 1 78 10.1186/1423‑0127‑17‑78 20868513
    [Google Scholar]
  52. Caselli C. Role of adiponectin system in insulin resistance. Mol. Genet. Metab. 2014 113 3 155 160 10.1016/j.ymgme.2014.09.003 25242063
    [Google Scholar]
  53. Andrade-Oliveira V. Câmara N.O.S. Moraes-Vieira P.M. Adipokines as drug targets in diabetes and underlying disturbances. J. Diabetes Res. 2015 2015 1 11 10.1155/2015/681612 25918733
    [Google Scholar]
  54. Beltowski J. Leptin and atherosclerosis. Atherosclerosis 2006 189 1 47 60 10.1016/j.atherosclerosis.2006.03.003 16580676
    [Google Scholar]
  55. Dallinga-Thie G.M. Dullaart R.P.F. Do genome-wide association scans provide additional information on the variation of plasma adiponectin concentrations? Atherosclerosis 2010 208 2 328 329 10.1016/j.atherosclerosis.2009.12.014 20053404
    [Google Scholar]
  56. Blüher M. Mantzoros C.S. From leptin to other adipokines in health and disease: Facts and expectations at the beginning of the 21st century. Metabolism 2015 64 1 131 145 10.1016/j.metabol.2014.10.016 25497344
    [Google Scholar]
  57. Finucane F.M. Luan J. Wareham N.J. Sharp S.J. O’Rahilly S. Balkau B. Flyvbjerg A. Walker M. Højlund K. Nolan J.J. Savage D.B. Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia 2009 52 11 2345 2349 10.1007/s00125‑009‑1508‑3 19756488
    [Google Scholar]
  58. Dullaart R.P.F. Gruppen E.G. Connelly M.A. Otvos J.D. Lefrandt J.D. GlycA, a biomarker of inflammatory glycoproteins, is more closely related to the leptin/adiponectin ratio than to glucose tolerance status. Clin. Biochem. 2015 48 12 811 814 10.1016/j.clinbiochem.2015.05.001 25977069
    [Google Scholar]
  59. Thomas S. Suresh S. Sudheesh M. Vijayakumar T. Association of insulin resistance with adipocytokine levels in patients with metabolic syndrome. Indian J. Clin. Biochem. 2015 30 2 155 160 10.1007/s12291‑014‑0423‑7 25883422
    [Google Scholar]
  60. Grisouard J. Dembinski K. Mayer D. Keller U. Müller B. Christ-Crain M. Targeting AMP-activated protein kinase in adipocytes to modulate obesity-related adipokine production associated with insulin resistance and breast cancer cell proliferation. Diabetol. Metab. Syndr. 2011 3 1 16 10.1186/1758‑5996‑3‑16 21774820
    [Google Scholar]
  61. Ruderman N.B. Carling D. Prentki M. Cacicedo J.M. AMPK, insulin resistance, and the metabolic syndrome. J. Clin. Invest. 2013 123 7 2764 2772 10.1172/JCI67227 23863634
    [Google Scholar]
  62. Drummond M.J. Rasmussen B.B. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr. Opin. Clin. Nutr. Metab. Care 2008 11 3 222 226 10.1097/MCO.0b013e3282fa17fb 18403916
    [Google Scholar]
  63. Coughlan K.A. Valentine R.J. Ruderman N.B. Saha A.K. Nutrient Excess in AMPK Downregulation and Insulin Resistance. J Endocrinol Diabetes Obes. 2013 1 1 1008
    [Google Scholar]
  64. Kwon H. Pessin J.E. Adipokines mediate inflammation and insulin resistance. Front. Endocrinol. (Lausanne) 2013 4 71 10.3389/fendo.2013.00071 23781214
    [Google Scholar]
  65. Yamauchi T. Kamon J. Minokoshi Y. Ito Y. Waki H. Uchida S. Yamashita S. Noda M. Kita S. Ueki K. Eto K. Akanuma Y. Froguel P. Foufelle F. Ferre P. Carling D. Kimura S. Nagai R. Kahn B.B. Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 2002 8 11 1288 1295 10.1038/nm788 12368907
    [Google Scholar]
  66. Liu Y. Turdi S. Park T. Morris N.J. Deshaies Y. Xu A. Sweeney G. Adiponectin corrects high-fat diet-induced disturbances in muscle metabolomic profile and whole-body glucose homeostasis. Diabetes 2013 62 3 743 752 10.2337/db12‑0687 23238294
    [Google Scholar]
  67. Lian K. Du C. Liu Y. Zhu D. Yan W. Zhang H. Hong Z. Liu P. Zhang L. Pei H. Zhang J. Gao C. Xin C. Cheng H. Xiong L. Tao L. Impaired adiponectin signaling contributes to disturbed catabolism of branched-chain amino acids in diabetic mice. Diabetes 2015 64 1 49 59 10.2337/db14‑0312 25071024
    [Google Scholar]
  68. Katagiri R. Goto A. Budhathoki S. Yamaji T. Yamamoto H. Kato Y. Iwasaki M. Tsugane S. Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes. Sci. Rep. 2018 8 1 1043 10.1038/s41598‑018‑19388‑w 29348480
    [Google Scholar]
  69. Ouchi N. Parker J.L. Lugus J.J. Walsh K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 2011 11 2 85 97 10.1038/nri2921 21252989
    [Google Scholar]
  70. Rabe K. Lehrke M. Parhofer K.G. Broedl U.C. Adipokines and insulin resistance. Mol. Med. 2008 14 11-12 741 751 10.2119/2008‑00058.Rabe 19009016
    [Google Scholar]
  71. Yamauchi T. Kamon J. Waki H. Terauchi Y. Kubota N. Hara K. Mori Y. Ide T. Murakami K. Tsuboyama-Kasaoka N. Ezaki O. Akanuma Y. Gavrilova O. Vinson C. Reitman M.L. Kagechika H. Shudo K. Yoda M. Nakano Y. Tobe K. Nagai R. Kimura S. Tomita M. Froguel P. Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 2001 7 8 941 946 10.1038/90984 11479627
    [Google Scholar]
  72. Weyer C. Funahashi T. Tanaka S. Hotta K. Matsuzawa Y. Pratley R.E. Tataranni P.A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J. Clin. Endocrinol. Metab. 2001 86 5 1930 1935 10.1210/jcem.86.5.7463 11344187
    [Google Scholar]
  73. Hara K. Horikoshi M. Yamauchi T. Yago H. Miyazaki O. Ebinuma H. Imai Y. Nagai R. Kadowaki T. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care 2006 29 6 1357 1362 10.2337/dc05‑1801 16732021
    [Google Scholar]
  74. Yoon M.S. The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism. Nutrients 2016 8 7 405 10.3390/nu8070405 27376324
    [Google Scholar]
  75. Holeček M. Branched-chain amino acids in health and disease: metabolism, alterations in blood plasma, and as supplements. Nutr. Metab. (Lond.) 2018 15 1 33 10.1186/s12986‑018‑0271‑1 29755574
    [Google Scholar]
  76. Pallares-Méndez R. Aguilar-Salinas C.A. Cruz-Bautista I. del Bosque-Plata L. Metabolomics in diabetes, a review. Ann. Med. 2016 48 1-2 89 102 10.3109/07853890.2015.1137630 26883715
    [Google Scholar]
  77. Boulet M.M. Chevrier G. Grenier-Larouche T. Pelletier M. Nadeau M. Scarpa J. Prehn C. Marette A. Adamski J. Tchernof A. Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk. Am. J. Physiol. Endocrinol. Metab. 2015 309 8 E736 E746 10.1152/ajpendo.00231.2015 26306599
    [Google Scholar]
  78. Viollet B. Foretz M. Animal Models to Study AMPK. EXS 2016 107 441 469 10.1007/978‑3‑319‑43589‑3_18 27812991
    [Google Scholar]
/content/journals/emiddt/10.2174/0118715303305579241014112730
Loading
/content/journals/emiddt/10.2174/0118715303305579241014112730
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: Branched-chain amino acids ; adipokines ; mTOR ; vitamins ; diabetes mellitus ; insulin resistance
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test