Octubre-Diciembre 2018 76
ISSN 1317-987X


Monografías docentes
Resistencia a la insulina


  1. Samuel VT and Shulman GI. 2016. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 126: 12–22.
  2. http://www.idf.org
  3. Shulman GI. 2000. Cellular mechanisms of insulin resistance. J Clin Invest.106:171-6.
  4. Kahn BB and Flier JS. 2000. Obesity and insulin resistance. J Clin Invest.106: 473-81.
  5. Gutiérrez-Rodelo C, Roura-Guiberna A and Olivares-Reyes JA. 2017. Molecular Mechanisms of Insulin Resistance: An Update. Gac Med Mex. 153:197-209.
  6. Odegaard JI and Chawla A. 2013. Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis. Science. 339: 172-177.
  7. González-Mujica F. 2017. Insulina. Estructura, síntesis, secreción, depuración y degradación. (Revisión). Vitae Julio-Septiembre 2017 Nº 71. Disponible en: http:/vitae.ucv.ve/?modulo=articulo_pdf&n=5600&rv=134.
  8. González-Mujica F. 2017. Mecanismo de acción de la insulina (Revisión). Vitae Octubre-Diciembre 2017 Nª 72. Disponible en http://vitae.ucv.ve/?module=articulo_pdf&n=5653&rv=137.
  9. De Meyts P. 2016. The Insulin Receptor and Its Signal Transduction Network. De Groot LJ, Chrousos G, Dungan K, et al., editors. South Dartmouth (MA): MDText.com, Inc.; 2000.
  10. Cantley LC. 2002. The phosphoinositide 3-kinase pathway. Science 296:1655-1657.
  11. Thong FSL, Dugani CB and Klip A. 2005. Turning Signals On and Off: GLUT4 Traffic in the Insulin-Signaling Highway. Physiology 20: 271-284.
  12. Avruch J. 2007. MAP kinase pathways: the first twenty years. Biochim Biophys Acta 1773:1150-1160.
  13. Boucher J, Kleinridders A and Kahn CR. 2014. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol. 6(1).pii: a009191.
  14. Olivares-Reyes JA. 2012. Bases moleculares del síndrome metabólico y resistencia a la insulina. En: Garibay Nieto GN, García Velasco S, eds. Obesidad en la edad pediátrica: prevención y tratamiento. Ciudad de México: Corinter; p. 185-214.
  15.  Zick Y. 2005. Ser/Thr phosphorylation of IRS proteins: a molecular basis for insulin resistance. Sci STKE. 2005 (268):pe4.
  16. Montagnani M, Ravichandran LV, Chen H, Esposito DL and Quon MJ. 2002. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol Endocrinol. 16:1931-1942.
  17. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R and Zeiher AM. 1999. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 399: 601-605.
  18. Lee JH and Ragolia L. 2006. AKT phosphorylation is essential for insulin-induced relaxation of rat vascular smooth muscle cells. Am J Physiol Cell Physiol. 291: C1355-1365.
  19. Olivares-Reyes JA and Arellano-Plancarte A. 2008. Bases moleculares de las acciones de la insulina. Rev Edu Bioq. 27: 9-18.
  20. Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, White MF and Accili D. 2000. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J Clin Invest. 105: 199-205.
  21. Chavez JA, Knotts TA, Wang LP, Li G, Dobrowsky RT, Florant GL, and Summers SA. 2003. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. J Biol Chem. 278: 10297-10303.
  22. Ye J. 2013. Mechanisms of insulin resistance in obesity. Front Med. 7: 14-24.
  23. Park HS, Park JY and Yu R. 2005. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract. 69: 29-35.
  24. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL and Ferrante AW Jr. 2003. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 112: 1796-1808.
  25. Halberg N, Wernstedt-Asterholm I and Scherer PE. 2008. The adipocyte as an endocrine cell. Endocrinol Metab Clin North Am. 37: 753–768.
  26. Shoelson SE, Lee J and Goldfine AB. 2006. Inflammation and insulin resistance. J Clin Invest. 116: 1793-1801.
  27. Ouchi N, Parker JL, Lugus JJ and Walsh K. 2011. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 11: 85-97.
  28. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H and Flier JS. 2006. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 116: 3015-3025.
  29. Watanabe Y, Nagai Y and Takatsu K. 2013. Activation and regulation of the pattern recognition receptors in obesity-induced adipose tissue inflammation and insulin resistance. Nutrients. 5: 3757-3778.
  30. Holland WL, Bikman BT, Wang LP, Yuguang G, Sargent KM, Bulchand S, Knotts TA, Shui G, Clegg DJ, Wenk MR, Pagliassotti MJ, Scherer PE and Summers SA. 2011. Lipid-induced insulin resistance mediated by the proinflammatory receptor TLR4 requires saturated fatty acid-induced ceramide biosynthesis in mice. J Clin Invest. 121: 1858-1870.
  31. Pedersen BK. 2007. IL-6 signaling in exercise and disease. Biochem Soc Trans. 35: 1295–1297.
  32. Straub RH, Cutolo M, Buttgereit F and Pongratz G. 2010. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J Intern Med. 267: 543–560.
  33. Ye J and Keller JN. 2010. Regulation of energy metabolism by inflammation: a feedback response in obesity and calorie restriction. Aging (Albany NY) 2: 361–368.
  34. Onyango AN. 2018. Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance. Oxid Med Cell Longev. 2018: 4321714.
  35. Onyango AN. 2017. The Contribution of Singlet Oxygen to Insulin Resistance. Oxid Med Cell Longev. 2017: 8765972.
  36. Braakman I and Hebert DN. 2013. Protein folding in the endoplasmic reticulum. Cold Spring Harb Perspect Biol. 5: a013201.
  37. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Görgün C, Glimcher LH and Hotamisligil GS. 2004. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science. 306: 457-461.
  38. Yalcin A and Hotamisligil GS. 2013. Impact of ER protein homeostasis on metabolism. Diabetes. 62: 691-693.
  39. Gregor MF, Yang L, Fabbrini E, Mohammed BS, Eagon JC, Hotamisligil GS and Klein S. 2009. Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes. 58: 693-700.
  40. Ozawa K, Miyazaki M, Matsuhisa M, Takano K, Nakatani Y, Hatazaki M, Tamatani T, Yamagata K, Miyagawa J, Kitao Y, Hori O, Yamasaki Y and Ogawa S. 2005. The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes. 54: 657-663.
  41. Xiao C, Giacca A and Lewis GF. 2011. Sodium Phenylbutyrate, a Drug With Known Capacity to Reduce Endoplasmic Reticulum Stress, Partially Alleviates Lipid-Induced Insulin Resistance and β-Cell Dysfunction in Humans. Diabetes. 60: 918-924.
  42. Kars M, Yang L, Gregor MF, Mohammed BS, Pietka TA, Finck BN, Patterson BW, Horton JD, Mittendorfer B, Hotamisligil GS and Klein S. 2010. Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women. Diabetes. 59: 1899-1905.
  43. Lowell BB and Shulman GI. 2005. Mitochondrial dysfunction and type 2 diabetes. Science. 307: 384–387.
  44. Montgomery MK and Turner N. 2015. Mitochondrial dysfunction and insulin resistance: an update. Endocrine Connect. 4: R1-R15.
  45. Holloszy JO. 2009. Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance. Am J Clin Nutr. 89: 463S–466S.
  46. Pagel-Langenickel I, Bao J, Pang L and Sack MN. 2010. The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance. Endocr Rev. 31: 25–51.
  47. Muoio DM. 2010. Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused? Biochim Biophys Acta. 1801: 281–288.
  48. Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, Neschen S, White MF, Bilz S, Sono S, Pypaert M and Shulman GI. 2005. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest. 115: 3587–3593.
  49. Stump CS, Short KR, Bigelow ML, Schimke JM and Nair KS. 2003. Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. Proc Natl Acad Sci USA. 100: 7996–78001.
  50. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, Roden M, Gnaiger E, Nohl H, Waldhäusl W and Fürnsinn C. 2004. Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? Diabetes 53: 1052–1059.
  51. González-Mujica F. 2016. Drogas antidiabéticas diferentes de la insulina. Mecanismos de acción. Vitae, Abril-Junio Nº 66. Disponible en: http://vitae.ucv.ve/?module=articulo&rv=124&n=5316
  52. Ye J. 2007. Role of insulin in the pathogenesis of free fatty acid-induced insulin resistance in skeletal muscle. Endocr Metab Immune Disord Drug Targets. 7: 65–74.

Resistencia a la insulina
Mecanismo de acción de la insulina
Mecanismo molecular de la resistencia a la insulina
Inflamación y resistencia a la insulina
Estrés del retículo endoplasmático y resistencia a la insulina
Disfunción mitocondrial y resistencia a la insulina
Hiperinsulinismo y resistencia a la insulina

NOTA: Toda la información que se brinda en este artículo es de carácter investigativo y con fines académicos y de actualización para estudiantes y profesionales de la salud. En ningún caso es de carácter general ni sustituye el asesoramiento de un médico. Ante cualquier duda que pueda tener sobre su estado de salud, consulte con su médico o especialista.

Instituto de Medicina Tropical - Facultad de Medicina - Universidad Central de Venezuela.
Elaborado por el Centro de Análisis de Imágenes Biomédicas Computarizadas CAIBCO,
Este portal ha sido desarrollado gracias al apoyo del Fonacit