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Vascular Effects of Insulin: Implications for Hyperglycemia Management

Vascular Effects of Insulin: Implications for Hyperglycemia Management. Potential beneficial effects of insulin. Anti-inflammatory NF- κ B MCP-1 ICAM-1 CRP I κ B. Antithrombotic TF PAI-1. Mechanistic benefits of insulin. Vasodilatory + Platelet inhibitory

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Vascular Effects of Insulin: Implications for Hyperglycemia Management

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  1. Vascular Effects of Insulin: Implications for Hyperglycemia Management

  2. Potential beneficial effects of insulin Anti-inflammatory NF-κB MCP-1 ICAM-1 CRP IκB Antithrombotic TFPAI-1 Mechanistic benefits of insulin Vasodilatory + Platelet inhibitory NO release cAMPeNOS Anti-oxidative ROS Cardioprotective Neuroprotective Antiapoptotic Glucose lowering Dandona P et al. Am J Cardiol. 2007;99(suppl):15B-26.

  3. Insulin exerts dose-dependent vasodilatory effect on adenosine-stimulated myocardial blood flow N = 10 healthy men 20% 19% *†‡ *† MBF (mL/g per min) * *P < 0.001 vs basal; †P < 0.05 vs saline; ‡P < 0.05 vs insulin 1 mU Sundell J et al. Diabetes. 2002;51:1125-30.

  4. Insulin infusion improves myocardial blood flow in patients with T2DM and CAD N = 43 P = 0.045 P = 0.018 MBF (mL/g per min) P = 0.003 P = 0.043 Rest Adenosine Ischemic regions Non-ischemic regions *1 mU/kg per min IV Lautamäki R et al. Diabetes. 2006:55:511-6.

  5. Insulin reduces myocardial injury and post-ischemic apoptosis in dogs 12 24 * * 10 20 8 16 Infarct size/AAR(%) Apoptotic index(%) † † 6 12 † † 4 8 4 2 0 0 GK Low-dose I GK Low-dose I V GIK V GIK Infarct size Apoptosis *P < 0.05, †P < 0.01 vs vehicle V = vehicle; G = glucose; K = Potassium; I = Insulin Zhang H-X et al. J Cardiovasc Pharmacol. 2006;48:306-13.

  6. Insulin improves post-MI cardiac contractile function recovery in dogs GK GIK Low-I 2600 2400 † * * † † +LVdP/dtmax (mm Hg/s) * 2200 * † † † 2000 1800 0 Reperfusion Ischemia Pre-I-10 min 50 min 1 hr 2 hr 3 hr 4 hr Time V Zhang H-X et al. J Cardiovasc Pharmacol. 2006;48:306-13. *P < 0.05, †P < 0.01 vs vehicle

  7. Insulin infusion has anti-inflammatory and profibrinolytic effects N = 32 with acute STEMI, without hyperglycemia 25 7 * 6 20 5 15 PAI-1 (ng/mL) * 13%‡ 4 CRP (mg/L) 10 * 3 5 2 44%† 0 1 –5 0 7%‡ –10 –1 0 2 4 6 24 48 0 2 4 6 24 48 Time (hours) Control Insulin *P < 0.05 between groups; †Insulin vs control;‡Changes vs baselinePAI = plasminogen activator inhibitor Chaudhuri A et al. Circulation. 2004;109:849-54.

  8. Insulin infusion with normoglycemia decreases NF-B * N = 10 with obesity, without diabetes 140 120 100 Intranuclear NF-B,  from baseline(%) 80 60 40 20 0 0 2 4 6 Time (hours) Dextrose infusion Insulin infusion *P < 0.05 vs baseline Dandona P et al. J Clin Endocrinol Metab. 2001;86:3257-65.

  9. Intensive insulin reverses impaired platelet response in ACS patients with T2DM N = 76 Platelet response to NO with intensive IV insulin Platelet response to NO correlates with BG r = -0.31P = 0.007 P = 0.049 vs sc insulin 100 55 80 IV insulin 45 Platelet SNP response(% inhibition) 60 sc insulin 35 40 20 25 0 0 90 180 270 360 450 540 630 0 12 Admission blood glucose (mg/dL) Time (hours) SNP = sodium nitroprusside, a nitric oxide (NO) donor Worthley MI et al. J Am Coll Cardiol. 2007;49:304-10.

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