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Reviews/Commentaries/Position Statements

The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia

  1. Paresh Dandona, MD,
  2. Ahmad Aljada, PHD and
  3. Arindam Bandyopadhyay, MD
  1. From the Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York
    Diabetes Care 2003 Feb; 26(2): 516-519. https://doi.org/10.2337/diacare.26.2.516
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    While acute myocardial infarction and patients admitted to intensive care units carry a serious risk of mortality and morbidity, the concomitant occurrence of hyperglycemia enhances this risk. This has been established through various studies over the past decade (1–3). More recently, it has been shown that the treatment of these conditions with intravenous infusions of insulin results in marked improvements in clinical outcomes (3–5). While the normalization of blood glucose concentration may be one factor in the improvement of these outcomes, insulin may exert benefits of its own, independently of the plasma glucose concentrations.

    Both septicemia and acute myocardial infarction are inflammatory states with markedly enhanced catabolism. There may be hyperglycemia and an increase in plasma free fatty acid (FFA) concentrations in both of these conditions. Increased FFA concentrations are known to be associated with a deterioration of clinical outcomes and may have toxic effects of their own on vascular reactivity and on the myocardium (6–9). FFAs may have effects on endothelial nitric oxide (NO) production (6), prostacyclin production (10), and the stability of prostacyclin in plasma (11). FFAs may also induce a state of insulin resistance through the induction of protein kinase C and inflammation through the suppression of inhibitor κB (IκB) in the skeletal muscle (12). Proinflammatory changes are also induced in the mononuclear cells by FFAs as reflected in an increase in nuclear factor-κB (NF-κB), the major proinflammatory transcription factor, an increase in reactive oxygen species (ROS) generation, and an increase in p47 phox (13). Thus, the normalization of FFA concentrations by insulin may produce a benefit. Similarly, it can be argued that insulin administration may facilitate the uptake of glucose by insulin-responsive organs, including the myocardium, thus providing for their metabolic needs. These mechanisms are based on our understanding of insulin as a metabolic hormone.

    The last few years have witnessed the emergence of insulin in a new and a totally unexpected role. Recent data have shown that insulin has a profound, rapid, and potent anti-inflammatory effect at the cellular and molecular levels (14–17 similar to that observed with glucocorticoids both in vitro (18) and in vivo (19–21). Thus, insulin suppresses the proinflammatory transcription factor NF-κB and the expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), and the chemokine, monocyte chemotactic protein-1 (MCP-1), in human aortic endothelial cells in vitro (14,15). Since one of the initial steps in inflammation is the adhesion of the circulating leukocytes to the endothelium and, thereafter, the arrival of more leukocytes to the site through chemokine action (22,23), the suppression of these two mediators of inflammation is cardinal in exerting an anti-inflammatory effect. Furthermore, the suppression of NF-κB may potentially lead to the inhibition of other potent mediators, like early growth response-1 (VEGF), and proinflammatory cytokines, like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), both of which are secreted in response to endotoxin challenge (24).

    Recent observations in humans in vivo have also shown that a low-dose infusion of insulin into human subjects induces a significant acute anti-inflammatory effect within 2 h (16).

    Thus, insulin causes a suppression of intranuclear NF-κB and an induction of the cytosolic IκB; it also causes a suppression of ROS generation and the suppression of p47phox subunit of NADPH oxidase, the enzyme that converts molecular O2 to the superoxide radical. Plasma concentrations of soluble ICAM-1 and MCP-1 as well as those of C-reactive protein (CRP) are reduced following insulin. These effects indicate a general anti-inflammatory action and are similar to those described for glucocorticoids in vitro and in vivo. In addition to NF-κB suppression, insulin has been shown to suppress two other proinflammatory transcription factors, activator protein-1 (AP-1) (25) and early growth response-1 (Egr-1) (17). These actions are of great interest since Egr-1 regulates the expression of tissue factor (TF) (26) and plasminogen activator inhibitor-1 (PAI-1) (27). TF is expressed on the surface of macrophages and foam cells in the atherosclerotic plaque. The exposure of the foam cells to blood following the rupture of the atherosclerotic plaque triggers the activation of the extrinsic coagulation cascade through TF-mediated activation of factor VII, which eventually results in the conversion of prothrombin to thrombin. Thrombin is a potent platelet proaggregator and also converts fibrinogen to fibrin. This sets the stage for thrombosis following plaque rupture during the evolution of acute myocardial infarction (22,23,28,29). The suppression of PAI-1 by insulin also has potential benefits since PAI-1 is an inhibitor of fibrinolysis (30,31). Insulin may thus facilitate clot dissolution in acute myocardial infarction. These actions of insulin may have further subtle effects on inflammation since procoagulatory processes may trigger proinflammatory processes. Indeed, activated protein C, an anticoagulant, has been shown to have beneficial effects in septicemia (32).

    Insulin has recently also been shown to suppress AP-1 (25), a transcription factor that regulates the expression of matrix metalloproteinases (MMPs). MMPs are capable of lysing collagen and other matrix proteins and thereby allow the spread of inflammatory cells (33–36. They thus mediate the thinning and finally the rupture of the atherosclerotic plaque, which triggers thrombosis as described above. MMPs also mediate the initial intimal injury, which allows the monocytes to enter the subendothelial intima in between endothelial cells. The suppression of MMPs secondary to that of AP-1 would therefore be protective to the endothelium and to the fibrous cap of the plaque. This could be useful in the clinical setting of unstable angina, which is associated with the rupture of the atherosclerotic plaque. AP-1 and MMPs are also suppressed by glucocorticoids in vitro (37,38) and in vivo (19). Glucocorticoids also suppress Egr-1 and, more than likely therefore, TF and PAI-1 (39).

    One mechanism underlying the anti-inflammatory effect of insulin may be through the release of NO from the endothelium; NO is known to exert an anti-inflammatory effect (40). Insulin has also been shown to induce an increase in the expression of NO synthase (NOS), the enzyme that generates NO (41). The induction of NOS and the release of NO acutely impart to insulin a vasodilatory property through the action of NO on the vascular smooth muscle. A similar effect of insulin on platelets allows it to exert an anti-aggregatory effect. The platelet has NOS that is activated by insulin to induce the generation of NO. NO exerts its effects on vascular smooth muscle and platelets through the activation of guanylate cyclase, which generates cGMP from GTP (42–44). The vasodilatory and antiplatelet effects are clearly of importance in the treatment of acute myocardial infarction. It is also of interest that NO may mediate at least a part of the anti-inflammatory effect attributable to insulin since the coincubation of an NOS inhibitor, nitro-arginine, with insulin and human aortic endothelial cells neutralizes the suppressive effect of insulin on the expression of ICAM-1 by these cells (14).

    It should be mentioned that insulin sensitizers of the thiazolidinedione (TZD) class have been shown to exert anti-inflammatory effects including the suppression of NF-κB, ROS generation, and p47phox subunit in mononuclear cell (MNC) and plasma concentrations of ICAM-1, MCP-1, TNF-α, and CRP. More recently, rosiglitazone has been shown to suppress plasma MMP-9 concentrations in diabetes (45). While one expects their effects to be useful in chronic situations, it is relevant that their anti-inflammatory effects are observed in 3–7 days in humans in vivo. In an experimental model of acute myocardial infarction, even a single dose of rosiglitazone has been shown to reduce myocardial damage by 50% (46,47). Therefore, the potential anti-inflammatory effect of TZDs in acute clinical situations requires investigation.

    While insulin exerts a comprehensive anti-inflammatory effect of relevance to the treatment of different inflammatory conditions, as described above, it is remarkable that glucose exerts a powerful proinflammatory effect. Thus, the administration of 75 g of glucose orally results in an increase in ROS generation by the circulating polymorphonuclear leukocytes (PMNs) and MNCs, an increase in p47phox protein, and a fall in plasma α-tocopherol concentrations. In addition to causing an increase in lipid peroxidation as reflected in an increase in plasma concentration of thiobarbituric acid-reacting substances (TBARS) (48–52). Glucose has also been shown to exert other prothrombotic effects (53). Clearly, therefore, glucose induces acute oxidative stress. Glucose has also been shown recently to induce an increase in intranuclear NF-κB, a fall in cytosolic IκB, an increase in IκB kinase (IKK)-α and IKKβ (49). Glucose induces similar proinflammatory changes in endothelial cells in vitro (54). These changes are clearly proinflammatory. In addition, it has also been shown that a 75-g glucose challenge in normal subjects induces an increase in AP-1 activity in MNCs along with an increase in the expression of MMP-2 in MNCs and an increase in plasma concentrations of MMP-2 and MMP-9 (50). As described above, MMPs aid in the spread of inflammation and in mediating the rupture of the atherosclerotic plaque. Similarly, glucose induces an increase in Egr-1 and TF expression in MNCs and an increase in plasma concentration of TF. Thus, several of the effects of glucose are diametrically opposite to those of insulin in the context of inflammation. Glucose also causes abnormalities in vascular reactivity (55). This may affect vital organ perfusion adversely especially during situations of increased demand.

    These proinflammatory effects of glucose have also been demonstrated in vitro. The incubation of endothelial cells in high glucose concentrations results in ROS generation and an increase in intranuclear NF-κB (54,56,57). Similarly, the incubation of monocytic cell lines in high glucose concentrations results in the elevation of intranuclear NF-κB and AP-1 with an increase in the expression of the proinflammatory cytokine, TNF-α (58). These effects of glucose are clearly of clinical relevance since hyperglycemia at the time of admission to the hospital determines the mortality and the duration of admission to the hospital, independently of the primary diagnosis or the previous history of diabetes. Because this effect of hyperglycemia was demonstrated in a retrospective study, it is important that these data be confirmed in a prospective study. However, it is legitimate to consider the aggressive control of blood glucose concentrations with insulin in patients admitted to the hospital to determine whether the normalization of blood glucose concentrations in hyperglycemic subjects improves the clinical outcomes. Such a study would have both clinical and pharmaco-economic implications (59).

    These observations lead us into a new paradigm (60) in which glucose and possibly other macronutrients have a proinflammatory action, while the hormone secreted in response to their intake has an anti-inflammatory effect. This new paradigm facilitates and extends our understanding of normal physiology and pathophysiology and also provides us with novel potential therapeutic uses of insulin and the normalization of plasma glucose concentrations. On the basis of the above discussion, it should be clear that any elevation of plasma glucose concentration is likely to be proinflammatory and thus potentially harmful. Similarly, the administration of insulin is likely to be anti-inflammatory and, thus, may be clinically beneficial. Therefore, when we use insulin to control elevated blood glucose concentrations, we benefit from both the reduction in the toxic effect of glucose and the anti-inflammatory effect of insulin. The clinical applications of this new paradigm are just beginning to be discovered. The possibilities appear to be immense and promising.

    Footnotes

    • Address correspondence and reprint requests to Paresh Dandona, MD, PhD, Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, NY 14209. E-mail: pdandona{at}kaleidahealth.org.

      Received for publication 6 September 2002.

      A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • DIABETES CARE

    References

    1. ↵
      Oswald GA, Smith CC, Betteridge DJ, Yudkin JS: Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction. Br Med J (Clin Res Ed) 293:917–922, 1986
    2. Norhammar AM, Ryden L, Malmberg K: Admission plasma glucose: independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients. Diabetes Care 22:1827–1831, 1999
      OpenUrlAbstract/FREE Full Text
    3. ↵
      Van den berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R: Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367, 2001
      OpenUrlCrossRefPubMedWeb of Science
    4. Diaz R, Paolasso EA, Piegas LS, Tajer CD, Moreno MG, Corvalan R, Isea JE, Romero G: Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiologicos Latinoamerica) Collaborative Group. Circulation 98:2227–2234, 1998
      OpenUrlAbstract/FREE Full Text
    5. ↵
      Malmberg K, Ryden L, Hamsten A, Herlitz J, Waldenstrom A, Wedel H: Mortality prediction in diabetic patients with myocardial infarction: experiences from the DIGAMI study. Cardiovasc Res 34:248–253, 1997
      OpenUrlAbstract/FREE Full Text
    6. ↵
      Lundman P, Tornvall P, Nilsson L, Pernow J: A triglyceride-rich fat emulsion and free fatty acids but not very low density lipoproteins impair endothelium-dependent vasorelaxation. Atherosclerosis 159:35–41, 2001
      OpenUrlCrossRefPubMedWeb of Science
    7. Steinberg HO, Paradisi G, Hook G, Crowder K, Cronin J, Baron AD: Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production. Diabetes 49:1231–1238, 2000
      OpenUrlAbstract
    8. Oliver MF, Yates PA: Induction of ventricular arrhythmias by elevation of arterial free fatty acids in experimental myocardial infarction. Cardiology 56:359–364, 1971
      OpenUrlPubMedWeb of Science
    9. ↵
      Kurien VA, Yates PA, Oliver MF: The role of free fatty acids in the production of ventricular arrhythmias after acute coronary artery occlusion. Eur J Clin Invest 1:225–241, 1971
      OpenUrlPubMedWeb of Science
    10. ↵
      Jeremy JY, Mikhailidis DP, Dandona P: Simulating the diabetic environment modifies in vitro prostacyclin synthesis. Diabetes 32:217–221, 1983
      OpenUrlAbstract/FREE Full Text
    11. ↵
      Mikhailidis DP, Mikhailidis AM, Woollard ML, Dandona P: Protection of prostacyclin-like activity in human plasma-a non-enzymatic mechanism? Clin Sci (Lond) 62:177–181, 1982
      OpenUrlPubMed
    12. ↵
      Itani SI, Ruderman NB, Schmieder F, Boden G: Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51:2005–2011, 2002
      OpenUrlAbstract/FREE Full Text
    13. ↵
      Tripathy D, Aljada A, Ghanim H, Tufail S, Chaudhuri A, Dandona P: Acute elevation of plasma free fatty acids increases reactive oxygen species (ROS) generation by polymorphonuclear cells, induces nuclear factor-kappa B (NF-kB) and impairs brachial artery reactivity in healthy subjects (Abstract). Diabetes 51(Suppl. 2):A318, 2002
      OpenUrl
    14. ↵
      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 85:2572–2575, 2000
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      Aljada A, Ghanim H, Saadeh R, Dandona P: Insulin inhibits NFkappaB and MCP-1 expression in human aortic endothelial cells. J Clin Endocrinol Metab 86:450–453, 2001
      OpenUrlCrossRefPubMedWeb of Science
    16. ↵
      Dandona P, Aljada A, Mohanty P, Ghanim H, Hamouda W, Assian E, Ahmad S: 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, 2001
      OpenUrlCrossRefPubMedWeb of Science
    17. ↵
      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 87:1419–1422, 2002
      OpenUrlCrossRefPubMedWeb of Science
    18. ↵
      De Bosscher K, Schmitz ML, Vanden Berghe W, Plaisance S, Fiers W, Haegeman G: Glucocorticoid-mediated repression of nuclear factor-kappaB-dependent transcription involves direct interference with transactivation. Proc Natl Acad Sci U S A 94:13504–13509, 1997
      OpenUrlAbstract/FREE Full Text
    19. ↵
      Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P: Hydrocortisone suppresses intranuclear activator-protein-1 (AP-1) binding activity in mononuclear cells and plasma matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9). J Clin Endocrinol Metab 86:5988–5991, 2001
      OpenUrlCrossRefPubMedWeb of Science
    20. Aljada A, Ghanim H, Assian E, Mohanty P, Hamouda W, Garg R, Dandona P: Increased IkappaB expression and diminished nuclear NF-kappaB in human mononuclear cells following hydrocortisone injection. J Clin Endocrinol Metab 84:3386–3389, 1999
      OpenUrlCrossRefPubMed
    21. ↵
      Dandona P, Mohanty P, Hamouda W, Aljada A, Kumbkarni Y, Garg R: Effect of dexamethasone on reactive oxygen species generation by leukocytes and plasma interleukin-10 concentrations: a pharmacodynamic study. Clin Pharmacol Ther 66:58–65, 1999
      OpenUrlCrossRefPubMedWeb of Science
    22. ↵
      DiCorleto PE: Cellular mechanisms of atherogenesis. Am J Hypertens 6:314S–318S, 1993
      OpenUrlPubMed
    23. ↵
      Faruqi RM, DiCorleto PE: Mechanisms of monocyte recruitment and accumulation (Review Article). Br Heart J 69(Suppl. 1):S19–S29, 1993
    24. ↵
      Wilson M, Blum R, Dandona P, Mousa S: Effects in humans of intravenously administered endotoxin on soluble cell-adhesion molecule and inflammatory markers: a model of human diseases. Clin Exp Pharmacol Physiol 28:376–380, 2001
      OpenUrlCrossRefPubMedWeb of Science
    25. ↵
      Ghanim H, Mohanty P, Aljada A, Chowhan S, Tripathy D, Dandona P: Insulin reduces the pro-inflammatory transcription factor, activation protein-1 (AP-1), in mononuclear cells (MNC) and plasma matrix metalloproteinase-9 (MMP-9) concentration (Abstract). Diabetes 50(Suppl. 2):A408, 2001
      OpenUrl
    26. ↵
      Mackman N: Regulation of the tissue factor gene. FASEB J 9:883–889, 1995
      OpenUrlAbstract
    27. ↵
      Liu C, Yao J, Mercola D, Adamson E: The transcription factor EGR-1 directly transactivates the fibronectin gene and enhances attachment of human glioblastoma cell line U251. J Biol Chem 275:20315–20323, 2000
      OpenUrlAbstract/FREE Full Text
    28. ↵
      Kruth HS: Macrophage foam cells and atherosclerosis. Front Biosci 6:D429–D455, 2001
      OpenUrlCrossRefPubMed
    29. ↵
      Plenz G, Robenek H: Monocytes/macrophages in atherosclerosis. Eur Cytokine Netw 9:701–703, 1998
      OpenUrlPubMedWeb of Science
    30. ↵
      Rauch U, Osende J, Fuster V, Badimon J, Fayad Z, Chesebro J: Thrombus formation on atherosclerotic plaques: pathogenesis and clinical consequences. Ann Intern Med 134:224–238, 2001
      OpenUrlCrossRefPubMedWeb of Science
    31. ↵
      Dahlback B: Blood coagulation. Lancet 355:1627–1632, 2000
      OpenUrlCrossRefPubMedWeb of Science
    32. ↵
      Clarke RC, Johnston JR, Mayne EE: Meningococcal septicaemia: treatment with protein C concentrate. Intensive Care Med 26:471–473, 2000
      OpenUrlCrossRefPubMed
    33. ↵
      Freestone T, Turner RJ, Coady A, Higman DJ, Greenhalgh RM, Powell JT: Inflammation and matrix metalloproteinases in the enlarging abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 15:1145–1151, 1995
      OpenUrlAbstract/FREE Full Text
    34. Mun-Bryce S, Rosenberg GA: Gelatinase B modulates selective opening of the blood-brain barrier during inflammation. Am J Physiol 274:R1203–R1211, 1998
      OpenUrlAbstract/FREE Full Text
    35. Shapiro SD: Diverse roles of macrophage matrix metalloproteinases in tissue destruction and tumor growth. Thromb Haemost 82:846–849, 1999
      OpenUrlPubMedWeb of Science
    36. ↵
      Gum R, Lengyel E, Juarez J, Chen JH, Sato H, Seiki M, Boyd D: Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences. J Biol Chem 271:10672–10680, 1996
      OpenUrlAbstract/FREE Full Text
    37. ↵
      Gonzalez MV, Jimenez B, Berciano MT, Gonzalez-Sancho JM, Caelles C, Lafarga M, Munoz A: Glucocorticoids antagonize AP-1 by inhibiting the Activation/phosphorylation of JNK without affecting its subcellular distribution. J Cell Biol 150:1199–1208, 2000
      OpenUrlAbstract/FREE Full Text
    38. ↵
      Kylmaniemi M, Oikarinen A, Oikarinen K, Salo T: Effects of dexamethasone and cell proliferation on the expression of matrix metalloproteinases in human mucosal normal and malignant cells. J Dent Res 75:919–926, 1996
      OpenUrlAbstract/FREE Full Text
    39. ↵
      Hass R, Brach M, Gunji H, Kharbanda S, Kufe D: Inhibition of EGR-1 and NF-kappa B gene expression by dexamethasone during phorbol ester-induced human monocytic differentiation. Biochem Pharmacol 44:1569–1576, 1992
      OpenUrlCrossRefPubMed
    40. ↵
      Zeng G, Quon MJ: Insulin-stimulated production of nitric oxide is inhibited by wortmannin: direct measurement in vascular endothelial cells. J Clin Invest 98:894–898, 1996
      OpenUrlCrossRefPubMedWeb of Science
    41. ↵
      Aljada A, Dandona P: Effect of insulin on human aortic endothelial nitric oxide synthase. Metabolism 49:147–150, 2000
      OpenUrlCrossRefPubMedWeb of Science
    42. ↵
      Brune B, Hanstein K: Rapid reversibility of nitric oxide induced platelet inhibition. Thromb Res 90:83–91, 1998
      OpenUrlCrossRefPubMedWeb of Science
    43. Pohl U, Busse R: EDRF increases cyclic GMP in platelets during passage through the coronary vascular bed. Circ Res 65:1798–1803, 1989
      OpenUrlAbstract/FREE Full Text
    44. ↵
      Riddell DR, Owen JS: Nitric oxide and platelet aggregation. Vitam Horm 57:25–48, 1999
      OpenUrlPubMedWeb of Science
    45. ↵
      Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI: Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 106:679–684, 2002
      OpenUrlAbstract/FREE Full Text
    46. ↵
      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: In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone. Circulation 104:2588–2594, 2001
      OpenUrlAbstract/FREE Full Text
    47. ↵
      Wayman NS, Hattori Y, McDonald MC, Mota-Filipe H, Cuzzocrea S, Pisano B, Chatterjee PK, Thiemermann C: Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size. FASEB J 16:1027–1040, 2002
      OpenUrlAbstract/FREE Full Text
    48. ↵
      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 85:2970–2973, 2000
      OpenUrlCrossRefPubMedWeb of Science
    49. ↵
      Aljada A, Ghanim H, Mohanty P, Hofmeyer D, Tripathy D, Dandona P: Glucose activates nuclear factor-kb (NF-kb) pathway in mononuclear cells (MNC) and induces an increase in p47phox. subunit in MNC membranes (Abstract). Diabetes 51(Suppl. 2):A537, 2002
      OpenUrl
    50. ↵
      Aljada A, Ghanim H, Mohanty P, Syed T, Dandona P: 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 Endocrinol Metab In press
    51. Ceriello A, Bortolotti N, Motz E, Crescentini A, Lizzio S, Russo A, Tonutti L, Taboga C: Meal-generated oxidative stress in type 2 diabetic patients. Diabetes Care 21:1529–1533, 1998
      OpenUrlAbstract/FREE Full Text
    52. ↵
      Ceriello A, Bortolotti N, Motz E, Pieri C, Marra M, Tonutti L, Lizzio S, Feletto F, Catone B, Taboga C: Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia. Metabolism 48:1503–1508, 1999
      OpenUrlCrossRefPubMedWeb of Science
    53. ↵
      Ceriello A: Coagulation activation in diabetes mellitus: the role of hyperglycaemia and therapeutic prospects. Diabetologia 36:1119–1125, 1993
      OpenUrlCrossRefPubMedWeb of Science
    54. ↵
      Yorek MA, Dunlap JA: Effect of increased concentration of D-glucose or L-fucose on monocyte adhesion to endothelial cell monolayers and activation of nuclear factor-kappaB. Metabolism 51:225–234, 2002
      OpenUrlCrossRefPubMed
    55. ↵
      Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C, D’Onofrio F: Vascular effects of acute hyperglycemia in humans are reversed by L-arginine: evidence for reduced availability of nitric oxide during hyperglycemia. Circulation 95:1783–1790, 1997
      OpenUrlAbstract/FREE Full Text
    56. ↵
      Morigi M, Angioletti S, Imberti B, Donadelli R, Micheletti G, Figliuzzi M, Remuzzi A, Zoja C, Remuzzi G: Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion. J Clin Invest 101:1905–1915, 1998
      OpenUrlCrossRefPubMedWeb of Science
    57. ↵
      Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M: Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790, 2000
      OpenUrlCrossRefPubMedWeb of Science
    58. ↵
      Guha M, Bai W, Nadler JL, Natarajan R: Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem 275:17728–17739, 2000
      OpenUrlAbstract/FREE Full Text
    59. ↵
      Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE: Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 87:978–982, 2002
      OpenUrlCrossRefPubMedWeb of Science
    60. ↵
      Dandona P, Aljada A, Mohanty P: The anti-inflammatory and potential anti-atherogenic effect of insulin: a new paradigm. Diabetologia 45:924–930, 2002
      OpenUrlCrossRefPubMedWeb of Science
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    Diabetes Care: 26 (2)

    In this Issue

    February 2003, 26(2)
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    The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia
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    The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia
    Paresh Dandona, Ahmad Aljada, Arindam Bandyopadhyay
    Diabetes Care Feb 2003, 26 (2) 516-519; DOI: 10.2337/diacare.26.2.516

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    The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia
    Paresh Dandona, Ahmad Aljada, Arindam Bandyopadhyay
    Diabetes Care Feb 2003, 26 (2) 516-519; DOI: 10.2337/diacare.26.2.516
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