Skip to main content
SpringerLink
Log in

Stress-hyperglycemia, insulin and immunomodulation in sepsis

  • Chapter
Book cover Applied Physiology in Intensive Care Medicine 2

  • 4496 Accesses

Abstract

Stress-hyperglycemia and insulin resistance are exceedingly common in critically ill patients, particularly those with sepsis. Multiple pathogenetic mechanisms are responsible for this metabolic syndrome; however, increased release of pro-inflammatory mediators and counter-regulatory hormones may play a pivotal role. Recent data suggests that hyperglycemia may potentiate the pro-inflammatory response while insulin has the opposite effect. Furthermore, emerging evidence suggests that tight glycemic control will improve the outcome of critically ill patients. This paper reviews the pathophysiology of stress hyperglycemia in the critically ill septic patient and outlines a treatment strategy for the management of this disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Martin GS, Mannino DM, Eaton S, Moss M (2003) The epidemiology of sepsis in the nited States from 1979 through 2000. N Engl J Med 348:1546–1554

    Article  PubMed  Google Scholar 

  2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care. Crit Care Med 29:1303–1310

    Article  PubMed  CAS  Google Scholar 

  3. Friedman G, Silva E, Vincent JL (1998) Has the mortality of septic shock changed with time? Crit Care Med 26:2078–2086

    Article  PubMed  CAS  Google Scholar 

  4. Marik PE, Varon J (2001) Sepsis: state of the art. Dis Mon 47:463–532

    Article  Google Scholar 

  5. Bone RC (1996) Sir Isaac Newton, sepsis, SIRS and CARS. Crit Care Med 24:1125–1128

    Article  PubMed  CAS  Google Scholar 

  6. Bone RC, Sibbald WJ, Sprung CL (1992) The ACCP-SCCM Consensus Conference on sepsis and organ failure. Chest 101:1481–1483

    Article  PubMed  CAS  Google Scholar 

  7. Bone RC, Grodzin CJ, Balk RA (1997) Sepsis: a new hypothesis for patho- genesis of the disease process. Chest 112:235–243

    Article  PubMed  CAS  Google Scholar 

  8. Natanson C, Esposito CJ, Banks SM (1998) The sirens' songs of confirmatory sepsis trials: selection bias and sampling error. Crit Care Med 26:1927–1931

    Article  PubMed  CAS  Google Scholar 

  9. Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, Gerstenberger EP, Fitz Y, Danner RL, Natanson C (2002) Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 166:1197–1205

    Article  PubMed  Google Scholar 

  10. Dellinger RP (1999) Severe sepsis trials: Why have they failed? Minerva Anestesiol 65:340–345

    PubMed  CAS  Google Scholar 

  11. van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367

    Article  PubMed  Google Scholar 

  12. van den Berghe G, Wouters PJ, Bouillon R, Weekers F, Verwaest C, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P (2003) Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus gly- cemic control. Crit Care Med 31:359366

    Google Scholar 

  13. Marik PE, Zaloga GP (2002) Adrenal insufficiency in the critically ill: a new look at an old problem. Chest 122:1784–1796

    Article  PubMed  Google Scholar 

  14. Hart BB, Stanford GG, Ziegler MG, Lake CR, Chernow B (1989) Cate- cholamines: study of interspecies variation. Crit Care Med 17:12031218

    Article  Google Scholar 

  15. van den Berghe G (2002) Neuroendocrine pathobiology of chronic illness. Crit Care Clin 18:509–528

    Article  PubMed  Google Scholar 

  16. Siegel JH, Cerra FB, Coleman B, Giovannini I, Shetye M, Border JR, McMenamy RH (1979) Physiological and metabolic correlations in human sepsis. Invited commentary. Surgery 86:163–193

    CAS  Google Scholar 

  17. Clowes GH, Martin H, Walji S, Hirsch E, Gazitua R, Goodfellow R (1978) Blood insulin responses to blood glucose levels in high output sepsis and spetic shock. Am J Surg 135:577–583

    Article  PubMed  CAS  Google Scholar 

  18. Dahn MS, Jacobs LA, Smith S, Hans B, Lange MP, Mitchell RA, Kirkpatrick JR (1985) The relationship of insulin production to glucose metabolism in severe sepsis. Arch Surg 120:166–172

    Article  PubMed  CAS  Google Scholar 

  19. Mizock BA (2001) Alterations in fuel metabolism in critical illness hyper- glycemia. Best Pract Res Clin En- docrinol Metab 15:533–551

    Article  CAS  Google Scholar 

  20. Mehta VK, Hao W, Brooks-Worrell BM, Palmer JP (1994) Low-dose in- terleukin 1 and tumor necrosis factor individually stimulate insulin release but in combination cause suppression. Eur J Endocrinol 130:208–214

    Article  PubMed  CAS  Google Scholar 

  21. Shepard PR, Kahn BB (1999) Glucose transporters and insulin action. Implications for insulin resistance and diabetes mellitus. N Engl J Med 341:248257

    Google Scholar 

  22. Pessin JE, Saltiel AR (2000) Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest 106:165–169

    Article  PubMed  CAS  Google Scholar 

  23. McCowen KC, Malhotra A, Bistrian BR (2001) Stress-induced hyperglycemia. Crit Care Clin 17:107–124

    Article  PubMed  CAS  Google Scholar 

  24. Frankenfield DC, Omert LA, Badellino MM, Wiles CE, III, Bagley SM, Goodarzi S, Siegel JH (1994) Correlation between measured energy expenditure and clinically obtained variables in trauma and sepsis patients. J Parenter Enteral Nutr 18:398–403

    Article  CAS  Google Scholar 

  25. Agwunobi AO, Reid C, Maycock P, Little RA, Carlson GL (2000) Insulin resistance and substrate utilization in human endotoxemia. J Clin En- docrinol Metab 85:3770–3778

    Article  CAS  Google Scholar 

  26. Gelb AW, Bayona NA, Wilson JX, Cechetto DF (2002) Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiol 96:1183–1190

    Article  CAS  Google Scholar 

  27. Sakurai Y, Zhang XJ, Wolfe RR (1996) TNF directly stimulates glucose uptake and leucine oxidation and inhibits FFA flux in conscious dogs. Am J Physiol 270:E864-E872

    PubMed  CAS  Google Scholar 

  28. Lang CH, Dobrescu C (1991) Gramnegative infection increases noninsulin-mediated glucose disposal. Endocrinology 128:645–653

    Article  PubMed  CAS  Google Scholar 

  29. Meszaros K, Lang CH, Bagby GJ, Spitzer JJ (1987) Tumor necrosis factor increases in vivo glucose utilization of macrophage-rich tissues. Bio- chem Biophys Res Commun 149:1–6

    Article  CAS  Google Scholar 

  30. Bird TA, Davies A, Baldwin SA, Saklatvala J (1990) Interleukin 1 stimulates hexose transport in fibro- blasts by increasing the expression of glucose transporters. J Biol Chem 265:13578–13583

    PubMed  CAS  Google Scholar 

  31. Green CJ, Campbell IT, O'Sullivan E, Underhill S, McLaren DP, Hipkin LJ, MacDonald IA, Russell J (1995) Septic patients in multiple organ failure can oxidize infused glucose, but non- oxidative disposal (storage) is impaired. Clin Sci 89:601–609

    PubMed  CAS  Google Scholar 

  32. Saeed M, Carlson GL, Little RA, Irving MH (1999) Selective impairment of glucose storage in human sepsis. Br J Surg 86:813–821

    Article  PubMed  CAS  Google Scholar 

  33. Mizock BA (1997) Alterations in fuel metabolism in critical illness. Hyper- glycemia. In: Ober KP (ed) Endocrinology of critical disease. Humana Press, Totawa, New Jersey, pp 197297

    Google Scholar 

  34. Mesotten D, Delhanty PJ, Vanderhoy- donc F, Hardman KV, Weekers F, Baxter RC, Van den BG (2002) Regulation of insulin-like growth factor binding protein-1 during protracted critical illness. J Clin Endocrinol Me- tab 87:5516–5523

    Article  CAS  Google Scholar 

  35. Jeevanandam M, Young DH, Schiller WR (1990) Glucose turnover, oxidation, and indices of recycling in severely traumatized patients. J Trauma 30:582–589

    Article  PubMed  CAS  Google Scholar 

  36. Cerra FB (1987) Hypermetabolism, organ failure, and metabolic support. Surgery 101:1–14

    PubMed  CAS  Google Scholar 

  37. Wolfe RR (1997) Substrate utilization/ insulin resistance in sepsis/trauma. Baillieres Clin Endocrinol Metab 11:645–657

    Article  PubMed  CAS  Google Scholar 

  38. Petit F, Bagby GJ, Lang CH (1995) Tumor necrosis factor mediates zy- mosan-induced increase in glucose flux and insulin resistance. Am J Physiol 268:E219-E228

    PubMed  CAS  Google Scholar 

  39. Roh MS, Moldawer LL, Ekman LG, Dinarello CA, Bistrian BR, Jeevanandam M, Brennan MF (1986) Stimulatory effect of interleukin-1 upon hepatic metabolism. Metabolism 35:419–424

    Article  PubMed  CAS  Google Scholar 

  40. Lang CH (1992) Sepsis-induced insulin resistance in rats is mediated by a beta-adrenergic mechanism. Am J Physiol 263:E703-E711

    PubMed  CAS  Google Scholar 

  41. Chambrier C, Laville M, Rhzioual BK, Odeon M, Bouletreau P, Beylot M (2000) Insulin sensitivity of glucose and fat metabolism in severe sepsis. Clin Sci 99:321–328

    Article  PubMed  CAS  Google Scholar 

  42. Aljada A, Ghanim H, Assian E, Dandona P (2002) Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial nitric oxide synthase and reduces insulin receptor content and phosphorylation in human aortic endothelial cells. Metabolism 51:487–491

    Article  PubMed  CAS  Google Scholar 

  43. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271:665668

    Article  Google Scholar 

  44. Kanety H, Feinstein R, Papa MZ, Hemi R, Karasik A (1995) Tumor necrosis factor alpha-induced phos- phorylation of insulin receptor sub- strate-1 (IRS-1). Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. J Biol Chem 270:23780–23784

    Article  PubMed  CAS  Google Scholar 

  45. Paz K, Hemi R, LeRoith D, Karasik A, Elhanany E, Kanety H, Zick Y (1997) A molecular basis for insulin resistance. Elevated serine/threonine phos- phorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamem- brane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphoryla- tion. J Biol Chem 272:29911–29918

    Article  PubMed  CAS  Google Scholar 

  46. Nunes AL, Carvalheira JB, Carvalho CR, Brenelli SL, Saad MJ (2001) Tissue-specific regulation of early steps in insulin action in septic rats. Life Sci 69:2103–2112

    Article  PubMed  CAS  Google Scholar 

  47. Hotamisligil GS, Budavari A, Murray D, Spiegelman BM (1994) Reduced tyrosine kinase activity of the insulin receptor in obesity-diabetes. Central role of tumor necrosis factor-alpha. J Clin Invest 94:1543–9

    CAS  Google Scholar 

  48. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM (1994) Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci USA 91:4854–4858

    Article  PubMed  CAS  Google Scholar 

  49. Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon MJ, Ye J (2002) Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem 277:48115–48121

    Article  PubMed  CAS  Google Scholar 

  50. Gay NJ, Keith FJ (1991) Drosophila Toll and IL-1 receptor. Nature 351:355–356

    Article  PubMed  CAS  Google Scholar 

  51. Belvin MP, Anderson KV (1996) A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu Rev Cell Develop Biol 12:393–416

    Article  CAS  Google Scholar 

  52. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S (1999) Cutting edge: Tolllike receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccha- ride: evidence for TLR4 as the Lps gene product. J Immunol 162:37493752

    Google Scholar 

  53. Barnes PJ, Karin M (1997) Nuclear factor-kB-A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071

    Article  PubMed  CAS  Google Scholar 

  54. Chiasson JL, Shikama H, Chu DT, Exton JH (1981) Inhibitory effect of epinephrine on insulin-stimulated glucose uptake by rat skeletal muscle. J Clin Invest 68:706–713

    Article  PubMed  CAS  Google Scholar 

  55. Haring H, Kirsch D, Obermaier B, Ermel B, Machicao F (1986) Decreased tyrosine kinase activity of insulin receptor isolated from rat adi- pocytes rendered insulin-resistant by catecholamine treatment in vitro. Biochem J 234:59–66

    PubMed  CAS  Google Scholar 

  56. Dimitriadis G, Leighton B, Parry- Billings M, Sasson S, Young M, Krause U, Bevan S, Piva T, Wegener G, ANewsholme EA (1997) Effects of glucocorticoid excess on the sensitivity of glucose transport and metabolism to insulin in rat skeletal muscle. Biochem J 321:707–712

    PubMed  CAS  Google Scholar 

  57. Smith TR, Elmendorf JS, David TS, Turinsky J (1997) Growth hormone- induced insulin resistance: role of the insulin receptor, IRS-1, GLUT-1, and GLUT-4. Am J Physiol 272:E1071- E1079

    PubMed  CAS  Google Scholar 

  58. Dominici FP, Cifone D, Bartke A, Turyn D (1999) Alterations in the early steps of the insulin-signaling system in skeletal muscle of GH- transgenic mice. Am J Physiol 277:E447-E454

    PubMed  CAS  Google Scholar 

  59. Khaodhiar L, McCowen K, Bistrian B (1999) Perioperative hyperglycemia, infection or risk? Curr Opin Clin Nutr Metab Care 2:79–82

    Article  PubMed  CAS  Google Scholar 

  60. Norhammar AM, Ryden L, Malmberg K (1999) Admission plasma glucose. Independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients. Diabetes Care 22:1827–1831

    CAS  Google Scholar 

  61. Zindrou D, Taylor KM, Bagger JP (2001) Admission plasma glucose: an independent risk factor in nondiabetic women after coronary artery bypass grafting. Diabetes Care 24:1634–1639

    Article  PubMed  CAS  Google Scholar 

  62. Malmberg K, Norhammar A, Wedel H, Ryden L (1999) Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long- term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation 99:2626–26232

    PubMed  CAS  Google Scholar 

  63. Malmberg K (1997) Prospective randomised study of intensive insulin treatment on long-term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. Br Med J 314:15121515

    Google Scholar 

  64. Malmberg K, Ryden L, Efendic S, Herlitz J, Nicol P, Waldenstrom A, Wedel H, Welin L (1995) 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 26:57–65

    Article  PubMed  CAS  Google Scholar 

  65. Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 32:24262432

    Article  Google Scholar 

  66. Woo J, Lam CW, Kay R, Wong AH, Teoh R, Nicholls MG (1990) The influence of hyperglycemia and diabetes mellitus on immediate and 3- month morbidity and mortality after acute stroke. Arch Neurol 47:11741177

    Article  Google Scholar 

  67. Dandona P, Aljada A, Bandyopadhyay A (2003) The potential therapeutic role of insulin in acute myocardial infarction in patients admitted to intensive care and in those with unspecified hyperglycemia. Diabetes Care 26:516–519

    Article  PubMed  Google Scholar 

  68. Hansen TK, Thiel S, Wouters PJ, Christiansen JS, van den Berghe G (2003) Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels. J Clin Endocrinol Metab 88:1082–1088

    Article  PubMed  CAS  Google Scholar 

  69. Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P (2000) Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab 85:2970–2973

    Article  PubMed  CAS  Google Scholar 

  70. Straczkowski M, Dzienis- Straczkowska S, Stepien A, Kowalska I, Szelachowska M, Kinalska I (2002) Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. J Clin Endocrinol Metab 87:4602–4606

    Article  PubMed  CAS  Google Scholar 

  71. Chettab K, Zibara K, Belaiba SR, McGregor JL (2002) Acute hypergly- caemia induces changes in the transcription levels of 4 major genes in human endothelial cells: macroarrays- based expression analysis. Thromb Haemost 87:141–148

    PubMed  CAS  Google Scholar 

  72. Standiford TJ, Kunkel SL, Green- berger MJ, Laichalk LL, Strieter RM (1996) Expression and regulation of chemokines in bacterial pneumonia. J Leukoc Biol 59:24–28

    PubMed  CAS  Google Scholar 

  73. Hack CE, Aarden LA, Thijs LG (1997) Role of cytokines in sepsis. Adv Immunol 66:101–195

    Article  PubMed  CAS  Google Scholar 

  74. Multz AS, Cohen R (2003) Systemic response to pneumonia in the critically ill patient. Semin Resp Infect 18:6871

    Google Scholar 

  75. Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P (2002) Glucose activates nuclear factor kappa B pathway in mononuclear cells (MNC) and induces an increase in p47phox. subunit in MNC membranes [Abstract]. Diabetes 51 (Suppl 2):A537

    Google Scholar 

  76. Yorek MA, Dunlap JA (2002) Effect of increased concentration of D-glu- cose or L-fucose on monocyte adhesion to endothelial cell monolayers and activation of nuclear factor-kap- paB. Metabolism 51:225–234

    Article  PubMed  CAS  Google Scholar 

  77. Guha M, Bai W, Nadler JL, Natarajan R (2000) Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hy- perglycemia-induced oxidant stress- dependent and -independent pathways. J Biol Chem 275:17728–17739

    Article  PubMed  CAS  Google Scholar 

  78. Ceriello A, Bortolotti N, Motz E, Pieri C, Marra M, Tonutti L, Lizzio S, Feletto F, Catone B, Taboga C (1999) Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyper- glycemia. Metabolism 48:1503–1508

    Article  PubMed  CAS  Google Scholar 

  79. Ceriello A (1993) Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia 36:1119–1125

    Article  PubMed  CAS  Google Scholar 

  80. Aljada A, Ghanim H, Mohanty P, Syed T, Dandona P (2003) Glucose intake induces an increase in AP-1 and Egr-1 in mononuclear cells and plasma matrix metalloproteinases and tissue factor (TF) concentrations. J Clin En- docrinol Metab

    Google Scholar 

  81. Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C, D'Onofrio F (1997) Vascular effects of acute hy- perglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hy- perglycemia. Circulation 95:17831790

    Google Scholar 

  82. Pozzilli P, Leslie RD (1994) Infections and diabetes: mechanisms and prospects for prevention. Diabet Med 11:935–941

    Article  PubMed  CAS  Google Scholar 

  83. Mowlavi A, Andrews K, Milner S, Herndon DN, Heggers JP (2000) The effects of hyperglycemia on skin graft survival in the burn patient. Ann Plast Surg 45:629–632

    Article  PubMed  CAS  Google Scholar 

  84. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A (1999) Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 67:352–360

    Article  PubMed  CAS  Google Scholar 

  85. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A (1997) Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 63:356–361

    Article  PubMed  CAS  Google Scholar 

  86. McManus LM, Bloodworth RC, Prihoda TJ, Blodgett JL, Pinckard RN (2001) Agonist-dependent failure of neutrophil function in diabetes correlates with extent of hyperglycemia. J Leukoc Biol 70:395–404

    PubMed  CAS  Google Scholar 

  87. Evans TW (2001) Hemodynamic and metabolic therapy in critically ill patients. N Engl J Med 345:1417–1418

    Article  PubMed  CAS  Google Scholar 

  88. Rassias AJ, Marrin CA, Arruda J, Whalen PK, Beach M, Yeager MP (1999) Insulin infusion improves neu- trophil function in diabetic cardiac surgery patients. Anesth Analg 88:1011–1016

    PubMed  CAS  Google Scholar 

  89. Nielson CP, Hindson DA (1989) Inhibition of polymorphonuclear leukocyte respiratory burst by elevated glucose concentrations in vitro. Diabetes 38:1031–1035

    Article  PubMed  CAS  Google Scholar 

  90. Kwoun MO, Ling PR, Lydon E, Im- rich A, Qu Z, Palombo J, Bistrian BR (1997) Immunologic effects of acute hyperglycemia in nondiabetic rats. J Parenter Enteral Nutr 21:91–95

    Article  CAS  Google Scholar 

  91. Dandona P, Aljada A, Mohanty P, Ghanim H, Hamouda W, Assian E, Ahmad S (2001) 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 86:3257–3265

    Article  PubMed  CAS  Google Scholar 

  92. Aljada A, Ghanim H, Mohanty P, Kapur N, Dandona P (2002) Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mono- nuclear cells (MNC) and reduces plasma tissue factor (TF) and plasmi- nogen activator inhibitor-1 (PAI-1) concentrations. J Clin Endocrinol Me- tab 87:1419–1422

    Article  CAS  Google Scholar 

  93. Aljada A, Dandona P (2000) Effect of insulin on human aortic endothelial nitric oxide synthase. Metabolism 49:147–150

    Article  PubMed  CAS  Google Scholar 

  94. Peng HB, Spiecker M, Liao JK (1998) Inducible nitric oxide: an autoregula- tory feedback inhibitor of vascular inflammation. J Immunol 161:19701976

    Google Scholar 

  95. Spiecker M, Darius H, Kaboth K, Hubner F, Liao JK (1998) Differential regulation of endothelial cell adhesion molecule expression by nitric oxide donors and antioxidants. J Leukoc Biol 63:732–739

    PubMed  CAS  Google Scholar 

  96. Spiecker M, Peng HB, Liao JK (1997) Inhibition of endothelial vascular cell adhesion molecule-1 expression by nitric oxide involves the induction and nuclear translocation of IkappaBalpha. J Biol Chem 272:30969–30974

    Article  PubMed  CAS  Google Scholar 

  97. Meldrum DR, McIntyre RC, Sheridan BC, Cleveland JC Jr, Fullerton DA, Harken AH (1997) L-arginine decreases alveolar macrophage proin- flammatory monokine production during acute lung injury by a nitric oxide synthase-dependent mechanism. J Trauma 43:888–893

    Article  PubMed  CAS  Google Scholar 

  98. Laroux FS, Lefer DJ, Kawachi S, Scalia R, Cockrell AS, Gray L, van der Heyde H, Hoffman JM, Grisham MB (2000) Role of nitric oxide in the regulation of acute and chronic inflammation. Antioxidants Redox Signaling 2:391–396

    Article  PubMed  CAS  Google Scholar 

  99. Torre A de la, Schroeder RA, Punzalan C, Kuo PC (1999) Endotoxin-mediat- ed S-nitrosylation of p50 alters NF- kappa B-dependent gene transcription in ANA-1 murine macrophages. J Immunol 162:4101–4108

    Google Scholar 

  100. Walley KR, McDonald TE, Hi- gashimoto Y, Hayashi S (1999) Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. Am J Respir Crit Care Med 160:698–704

    PubMed  CAS  Google Scholar 

  101. Pahl HL (1999) Activators and target genes of rel/NF-kappaB transcription factors. Oncogene 18:6853–6866

    Article  PubMed  CAS  Google Scholar 

  102. Bohrer H, Qiu F, Zimmermann T, Zhang Y, Jllmer T, Mannel D, Bottiger BW, Stern DM, Waldherr R, Saeger HD, Ziegler R, Bierhaus A, Martin E, Nawroth PP (1997) Role of NFkappaB in the mortality of sepsis. J Clin Invest 100:972–985

    Article  PubMed  CAS  Google Scholar 

  103. Arnalich F, Garcia-Palomero E, Lopez J, Jimenez M, Madero R, Renart J, Vazquez JJ, Montiel C (2000) Predictive value of nuclear factor kappaB activity and plasma cytokine levels in patients with sepsis. Infect Immunol 68:1942–1945

    Article  CAS  Google Scholar 

  104. Paterson RL, Galley HF, Dhillon JK, Webster NR (2000) Increased nuclear factor kappa B activation in critically ill patients who die. Crit Care Med 28:1047–1051

    Article  PubMed  CAS  Google Scholar 

  105. Marik PE (2002) Nuclear factor-kap- paB inhibition in sepsis: steroids versus specific nuclear factor-kappaB inhibitors? Crit Care Med 30:2393–2394

    Article  PubMed  Google Scholar 

  106. Christman JW, Lancaster LH, Blackwell TS (1998) Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med 24:1131–1138

    Article  PubMed  CAS  Google Scholar 

  107. Fink MP (2003) Nulcear factor-kB: Is it a therapeutic target for the adjuvant treatment of sepsis. Crit Care Med 31:2400–2402

    Article  PubMed  Google Scholar 

  108. Liu SF, Ye X, Malik AB (1999) Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate prevents In vivo expression of proinflammatory genes. Circulation 100:1330–1337

    PubMed  CAS  Google Scholar 

  109. Marik PE, Zaloga G (2003) Gastric vs post-pyloric feeding? A systematic review. Intensive Care Med

    Google Scholar 

  110. Marik PE, Zaloga GP (2001) Early enteral nutrition in acutely ill patients: a systematic review. Crit Care Med 29:2264–2270

    Article  PubMed  CAS  Google Scholar 

  111. Marik PE, Pinsky MR (2003) Death by total parenteral nutrition. Intensive Care Med 29:867–869

    PubMed  Google Scholar 

  112. Ghanim H, Garg R, Aljada A, Mohanty P, Kumbkarni Y, Assian E, Hamouda W, Dandona P (2001) Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone: evidence for an anti-inflammatory effect and a potential an- tiatherosclerotic effect in the obese. J Clin Endocrinol Metab 86:13061312

    Article  Google Scholar 

  113. Aljada A, Garg R, Ghanim H, Mohanty P, Hamouda W, Assian E, Dandona P (2001) Nuclear factor- kappaB suppressive and inhibitor- kappaB stimulatory effects of trogli- tazone in obese patients with type 2 diabetes: evidence of an antiinflam- matory action? J Clin Endocrinol Metab 86:3250–3256

    Article  PubMed  CAS  Google Scholar 

  114. Yue Tl TL, Chen J, Bao W, Narayanan PK, Bril A, Jiang W, Lysko PG, Gu JL, Boyce R, Zimmerman DM, Hart TK, Buckingham RE, Ohlstein EH (2001) In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 104:2588–2594

    Article  PubMed  CAS  Google Scholar 

  115. Wayman NS, Hattori Y, McDonald MC, Mota-Filipe H, Cuzzocrea S, Pisano B, Chatteijee PK, Thiemer- mann C (2002) Ligands of the perox- isome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size. FASEB J 16:1027–1040

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Paul E. Marik

  2. Conemaugh Memorial Medical Center, Johnstown, PA, USA

    Murugan Raghavan

Authors
  1. Paul E. Marik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Murugan Raghavan
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dept. of Critical Care Medicine, University of Pittsburgh Medical Center, Scaife Hall 606 3550 Terrace Street, Pittsburgh, PA, 15261, USA

    Michael R. Pinsky MD

  2. Dept. Intensive Care Medicine, Hôpital Henri Mondor, 51 av. Maréchal Lattre de Tassigny, 94010, Créteil, CX, France

    Laurent Brochard MD

  3. Dept. Intensive Care Medicine, Hospital de Sant Pau, Avda. S. Antonio M. Claret 167, 08025, Barcelona, Spain

    Jordi Mancebo MD

  4. General Intensive Care Unit, Università Cattolica des Sacro Cuore, Largo A. Gemelli 8, 00168, Rome, Italy

    Massimo Antonelli

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Marik, P.E., Raghavan, M. (2012). Stress-hyperglycemia, insulin and immunomodulation in sepsis. In: Pinsky, M.R., Brochard, L., Mancebo, J., Antonelli, M. (eds) Applied Physiology in Intensive Care Medicine 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28233-1_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-28233-1_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-28232-4

  • Online ISBN: 978-3-642-28233-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation