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The Anti-Inflammatory and Antiatherogenic Effects of Insulin

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Cardiovascular Endocrinology

Part of the book series: Contemporary Endocrinology ((COE))

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Summary

The concept that insulin affects carbohydrate, lipid, and protein metabolism and that its deficiency leads to diabetes mellitus has given this hormone a central position as a key metabolic regulator. However, its role as a vasoactive hormone and as an inhibitor of inflammation and oxidative stress has been revealed over the past decade and a half. These discoveries are relevant to the understanding of the role of oxidative stress and inflammation in the pathogenesis of insulin resistance and why obesity and type 2 diabetes are proinflammatory and proatherogenic states. A direct antiatherogenic effect of insulin has now been demonstrated in mice with experimental atherogenesis, and mice with an interference with insulin signal transduction have been shown to be proatherogenic. The recent discovery that glucose and macronutrient intake induce oxidative stress and inflammation have added a new dimension to understanding of why obesity and type 2 diabetes are proinflammatory and proatherogenic. These data are now evolved enough for us to plan clinical strategies to use insulin as an anti-inflammatory agent in acute syndromes like acute myocardial infarction and in patients in surgical and medical intensive care units.

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References

  1. Grover A, Padginton C, Wilson MF, Sung BH, Izzo JL, Jr, Dandona P. Insulin attenuates norepinephrine-induced venoconstriction. An ultrasonographic study. Hypertension 1995;25:779–84.

    PubMed  CAS  Google Scholar 

  2. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994;94:1172–9.

    Article  PubMed  CAS  Google Scholar 

  3. Aljada A, Saadeh R, Assian E, Ghanim H, Dandona P. Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. J Clin Endocrinol Metab 2000;85:2572–5.

    Article  PubMed  CAS  Google Scholar 

  4. Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest 1996;98:894–8.

    Article  PubMed  CAS  Google Scholar 

  5. Aljada A, Dandona P. Effect of insulin on human aortic endothelial nitric oxide synthase. Metabolism 2000;49:147–50.

    Article  PubMed  CAS  Google Scholar 

  6. Aljada A, Ghanim H, Saadeh R, Dandona P. Insulin Inhibits NFkappaB and MCP-1 expression in human aortic endothelial cells. J Clin Endocrinol Metab 2001;86:450–453.

    Article  PubMed  CAS  Google Scholar 

  7. Dandona P, Aljada A, Mohanty P, et al. Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect? J Clin Endocrinol Metab 2001;86:3257–65.

    Article  PubMed  CAS  Google Scholar 

  8. Aljada A, Ghanim H, Mohanty P, Kapur N, Dandona P. Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. J Clin Endocrinol Metab 2002;87:1419–22.

    Article  PubMed  CAS  Google Scholar 

  9. Dandona P, Aljada A, Mohanty P, Ghanim H, Bandyopadhyay A, Chaudhuri A. Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9. Diabetes Care 2003;26:3310–4.

    Article  PubMed  CAS  Google Scholar 

  10. Weis S, Shintani S, Weber A, et al. Src blockade stabilizes a Flk/cadherin complex, reducing edema and tissue injury following myocardial infarction. J Clin Invest 2004;113:885–94.

    PubMed  CAS  Google Scholar 

  11. Chaudhuri A, Janicke D, Wilson MF, et al. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation 2004;109:849–54.

    Article  PubMed  CAS  Google Scholar 

  12. Koskenkari JK, Kaukoranta PK, Rimpilainen J, et al. Anti-inflammatory effect of high-dose insulin treatment after urgent coronary revascularization surgery. Acta Anaesthesiol Scand 2006;50:962–9.

    Article  PubMed  CAS  Google Scholar 

  13. Visser L, Zuurbier CJ, Hoek FJ, et al. Glucose, insulin and potassium applied as perioperative hyperinsulinaemic normoglycaemic clamp: effects on inflammatory response during coronary artery surgery. Br J Anaesth 2005;95:448–57.

    Article  PubMed  CAS  Google Scholar 

  14. Wong VW, McLean M, Boyages SC, Cheung NW. C-reactive protein levels following acute myocardial infarction: effect of insulin infusion and tight glycemic control. Diabetes Care 2004;27:2971–3.

    Article  PubMed  CAS  Google Scholar 

  15. Chaudhuri A, Janicke D, Wilson MF, Ghanim H, Aljada A, Dandona P. Free fatty acid suppressive, Pro- MMP-1 lowering and cardioprotective effect of insulin in STEMI. Diabetes 2005;54:A182:739-P.

    Google Scholar 

  16. Langouche L, Vanhorebeek I, Vlasselaers D, et al. Intensive insulin therapy protects the endothelium of critically ill patients. J Clin Invest 2005;115:2277–2286.

    Article  PubMed  CAS  Google Scholar 

  17. Herndon DN, Tompkins RG. Support of the metabolic response to burn injury. Lancet 2004;363:1895–902.

    Article  PubMed  CAS  Google Scholar 

  18. Jeschke MG, Einspanier R, Klein D, Jauch KW. Insulin attenuates the systemic inflammatory response to thermal trauma. Mol Med 2002;8:443–50.

    PubMed  CAS  Google Scholar 

  19. Andersson CX, Sopasakis VR, Wallerstedt E, Smith U. Insulin antagonizes IL-6 signaling and is anti-inflammatory in 3T3-L1 adipocytes. JBC 2007;282:9430–9435.

    Article  CAS  Google Scholar 

  20. Cheung NW, Wong VW, McLean M. The Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) study: a randomized controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care 2006;29:765–70.

    Article  PubMed  CAS  Google Scholar 

  21. Malmberg K, Ryden L, Efendic S, et al. Randomized trial of insulin–glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995;26:57–65.

    Article  PubMed  CAS  Google Scholar 

  22. Gao F, Gao E, Yue TL, et al. Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation. Circulation 2002;105:1497–502.

    Article  PubMed  CAS  Google Scholar 

  23. Jonassen AK, Brar BK, Mjos OD, Sack MN, Latchman DS, Yellon DM. Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism. J Mol Cell Cardiol 2000;32:757–64.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang HX, Zang YM, Huo JH, et al. Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs. J Cardiovasc Pharmacol 2006;48:306–13.

    Article  PubMed  CAS  Google Scholar 

  25. Griselli M, Herbert J, Hutchinson WL, et al. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999;190:1733–40.

    Article  PubMed  CAS  Google Scholar 

  26. Pepys MB, Hirschfield GM, Tennent GA, et al. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 2006;440:1217–21.

    Article  PubMed  CAS  Google Scholar 

  27. Bucciarelli-Ducci C, Bianchi M, De Luca L, et al. Effects of glucose–insulin–potassium infusion on myocardial perfusion and left ventricular remodeling in patients treated with primary angioplasty for ST-elevation acute myocardial infarction. Am J Cardiol 2006;98:1349–53.

    Article  PubMed  CAS  Google Scholar 

  28. Trovati M, Massucco P, Mattiello L, Mularoni E, Cavalot F, Anfossi G. Insulin increases guanosine-3′,5′-cyclic monophosphate in human platelets. A mechanism involved in the insulin anti-aggregating effect. Diabetes 1994;43:1015–9.

    Article  PubMed  CAS  Google Scholar 

  29. Trovati M, Anfossi G, Massucco P, et al. Insulin stimulates nitric oxide synthesis in human platelets and, through nitric oxide, increases platelet concentrations of both guanosine-3′, 5′-cyclic monophosphate and adenosine-3′, 5′-cyclic monophosphate. Diabetes 1997;46:742–9.

    Article  PubMed  CAS  Google Scholar 

  30. Worthley MI, Holmes AS, Willoughby SR, et al. The deleterious effects of hyperglycemia on platelet function in diabetic patients with acute coronary syndromes: mediation by superoxide production, resolution with intensive insulin administration. J Am Coll Cardiol 2007;49:304–310.

    Article  PubMed  CAS  Google Scholar 

  31. Libby P, Simon DI. Inflammation and thrombosis: the clot thickens. Circulation 2001;103:1718–20.

    PubMed  CAS  Google Scholar 

  32. Shamir R, Shehadeh N, Rosenblat M, et al. Oral insulin supplementation attenuates atherosclerosis progression in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2003;23:104–10.

    Article  PubMed  CAS  Google Scholar 

  33. Kubota T, Kubota N, Moroi M, et al. Lack of insulin receptor substrate-2 causes progressive neointima formation in response to vessel injury. Circulation 2003;107:3073–80.

    Article  PubMed  CAS  Google Scholar 

  34. Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999;340:115–26.

    Article  PubMed  CAS  Google Scholar 

  35. Dandona P, Aljada A, Mohanty P. The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 2002;45:924–30.

    Article  PubMed  CAS  Google Scholar 

  36. Han S, Liang CP, DeVries-Seimon T, et al. Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions. Cell Metab 2006;3:257–66.

    Article  PubMed  CAS  Google Scholar 

  37. Baumgartl J, Baudler S, Scherner M, et al. Myeloid lineage cell-restricted insulin resistance protects apolipoprotein E-deficient mice against atherosclerosis. Cell Metab 2006;3:247–56.

    Article  PubMed  CAS  Google Scholar 

  38. Nathan DM, Lachin J, Cleary P, et al. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 2003;348:2294–303.

    Article  PubMed  Google Scholar 

  39. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643–53.

    Article  PubMed  Google Scholar 

  40. Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab 2000;85:2970–3.

    Article  PubMed  CAS  Google Scholar 

  41. Dhindsa S, Tripathy D, Mohanty P, et al. Differential effects of glucose and alcohol on reactive oxygen species generation and intranuclear nuclear factor-kappaB in mononuclear cells. Metabolism 2004;53:330–4.

    Article  PubMed  CAS  Google Scholar 

  42. Esposito K, Nappo F, Marfella R, et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002;106:2067–72.

    Article  PubMed  CAS  Google Scholar 

  43. Aljada A, Ghanim H, Mohanty P, Syed T, Bandyopadhyay A, Dandona P. Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations. Am J Clin Nutr 2004;80:51–7.

    PubMed  CAS  Google Scholar 

  44. Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 2004;24:1015–22.

    Article  PubMed  CAS  Google Scholar 

  45. Steppich BA, Moog P, Matissek C, et al. Cytokine profiles and T cell function in acute coronary syndromes. Atherosclerosis 2007;190:443–51.

    Article  PubMed  CAS  Google Scholar 

  46. Ceriello A, Giacomello R, Stel G, et al. Hyperglycemia-induced thrombin formation in diabetes. The possible role of oxidative stress. Diabetes 1995;44:924–8.

    Article  PubMed  CAS  Google Scholar 

  47. Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P. Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr 2002;75:767–72.

    PubMed  CAS  Google Scholar 

  48. Tripathy D, Mohanty P, Dhindsa S, et al. Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects. Diabetes 2003;52:2882–7.

    Article  PubMed  CAS  Google Scholar 

  49. Aljada A, Mohanty P, Ghanim H, et al. Increase in intranuclear nuclear factor κB and decrease in inhibitor κB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Am J Clin Nutr 2004;79:682–690.

    PubMed  CAS  Google Scholar 

  50. Ghanim H, Aljada A, Hofmeyer D, Syed T, Mohanty P, Dandona P. Circulating mononuclear cells in the obese are in a proinflammatory state. Circulation 2004;110:1564–71.

    Article  PubMed  CAS  Google Scholar 

  51. Mohanty P, Daoud N, Ghanim H, et al. Absence of oxidative stress and inflammation following the intake of a 900 kcalorie meal rich in fruit and fiber. Diabetes 2004;53:A405.

    Google Scholar 

  52. Ghanim H, Mohanty P, Pathak R, Chaudhuri A, Sia CL, Dandona P. Orange juice or fructose intake does not induce oxidative and inflammatory Response. Diabetes Care 2007.

    Google Scholar 

  53. Dandona P, Mohanty P, Ghanim H, et al. The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation. J Clin Endocrinol Metab 2001;86:355–362.

    Article  PubMed  CAS  Google Scholar 

  54. Dandona P, Mohanty P, Hamouda W, et al. Inhibitory effect of a two day fast on reactive oxygen species (ROS) generation by leucocytes and plasma ortho-tyrosine and meta-tyrosine concentrations. J Clin Endocrinol Metab 2001;86:2899–902.

    Article  PubMed  CAS  Google Scholar 

  55. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998;83:2907–10.

    Article  PubMed  CAS  Google Scholar 

  56. Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111:1448–1454.

    Article  PubMed  Google Scholar 

  57. Dandona P, Mohanty P, Chaudhuri A, Garg R, Aljada A. Insulin infusion in acute illness. J Clin Invest 2005;115:2069–72.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Paresh Dandona
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  2. Ajay Chaudhuri
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  3. Husam Ghanim
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  4. Priya Mohanty
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Editors and Affiliations

  1. Tulane University Health Sciences Center, New Orleans, LO, USA

    Vivian A. Fonseca (MD) (MD)

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Dandona, P., Chaudhuri, A., Ghanim, H., Mohanty, P. (2009). The Anti-Inflammatory and Antiatherogenic Effects of Insulin. In: Fonseca, V.A. (eds) Cardiovascular Endocrinology. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-141-3_5

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  • DOI: https://doi.org/10.1007/978-1-59745-141-3_5

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-850-8

  • Online ISBN: 978-1-59745-141-3

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