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Molecular Medicine

, Volume 21, Issue 1, pp 68–76 | Cite as

Acute Hepatic Insulin Resistance Contributes to Hyperglycemia in Rats Following Myocardial Infarction

  • Jiali Wang
  • Baoshan Liu
  • Hui Han
  • Qiuhuan Yuan
  • Mengyang Xue
  • Feng Xu
  • Yuguo Chen
Research Article

Abstract

Although hyperglycemia is common in patients with acute myocardial infarction (MI), the underlying mechanisms are largely unknown. Insulin signaling plays a key role in the regulation of glucose homeostasis. In this study, we test the hypothesis that rapid alteration of insulin signaling pathways could be a potential contributor to acute hyperglycemia after MI. Male rats were used to produce MI by ligation of the left anterior descending coronary artery. Plasma glucose and insulin levels were significantly higher in MI rats than those in controls. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. However, insulin-stimulated signaling was not altered significantly in skeletal muscle after MI. The relative mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase were slightly higher in the liver tissue of MI rats than those in controls. Rosiglitazone (ROSI) markedly restored hepatic insulin signaling, inhibited gluconeogenesis and reduced plasma glucose levels in MI rats. Insulin resistance develops rapidly in liver but not skeletal muscle after MI, which contributes to acute hyperglycemia. Therapy aimed at potentiating hepatic insulin signaling may be beneficial for MI-induced hyperglycemia.

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (81170136,81100147,81300103,81300219), the Taishan Scholar Program of Shandong Province (ts20130911), the Specialized Research Fund for the Doctoral Program of Higher Education (20130131110048), a grant from Department of Science and Technology of Shandong Province (2011GSF11806) and the Shandong Provincial Outstanding Medical Academic Professional Program, 1020 Program from the Health Department of Shandong Province, China.

Supplementary material

10020_2015_2101068_MOESM1_ESM.pdf (650 kb)
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References

  1. 1.
    Stranders I, et al. (2004) Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus. Arch. Intern. Med. 164:982–8.CrossRefGoogle Scholar
  2. 2.
    Ishihara M. (2012) Acute hyperglycemia in patients with acute myocardial infarction. Circ. J. 76:563–71.CrossRefGoogle Scholar
  3. 3.
    Diaz R, et al. (2007) Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA. 298:2399–405.CrossRefGoogle Scholar
  4. 4.
    de Mulder M, et al. (2013) Intensive glucose regulation in hyperglycemic acute coronary syndrome: results of the randomized BIOMarker study to identify the acute risk of a coronary syndrome-2 (BIOMArCS-2) glucose trial. JAMA Intern. Med. 173:1896–904.CrossRefGoogle Scholar
  5. 5.
    Saltiel AR, Kahn CR. (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 414:799–806.CrossRefGoogle Scholar
  6. 6.
    Carrera BCA, Martinez-Moreno JM. (2013) Pathophysiology of diabetes mellitus type 2: beyond the duo “insulin resistance-secretion deficit.” Nutr. Hosp. 28 Suppl 2:78–87.Google Scholar
  7. 7.
    Zick Y. (2001) Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell. Biol. 11:437–41.CrossRefGoogle Scholar
  8. 8.
    Yi Z, et al. (2007) Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle. Diabetes. 56:1508–16.CrossRefGoogle Scholar
  9. 9.
    Truglia JA, Livingston JN, Lockwood DH. (1985) Insulin resistance: receptor and post-binding defects in human obesity and non-insulin-dependent diabetes mellitus. Am. J. Med. 79:13–22.CrossRefGoogle Scholar
  10. 10.
    Liu YF, et al. (2001) Insulin stimulates PKCzeta — mediated phosphorylation of insulin receptor substrate-1 (IRS-1). A self-attenuated mechanism to negatively regulate the function of IRS proteins. J. Biol. Chem. 276:14459–65.CrossRefGoogle Scholar
  11. 11.
    Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research, Division on Earth and Life Studies, National Research Council of the National Academies. (2011) Guide for the Care and Use of Laboratory Animals. 8th edition. Washington (DC): National Academies Press.Google Scholar
  12. 12.
    Su H, et al. (2007) Acute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK. Am. J. Physiol. Endocrinol. Metab. 293:E629–35.CrossRefGoogle Scholar
  13. 13.
    Wang J, et al. (2011) Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats. Mol. Med. 17:172–9.PubMedGoogle Scholar
  14. 14.
    Morgan DO, Roth RA. (1987) Acute insulin action requires insulin receptor kinase activity: introduction of an inhibitory monoclonal antibody into mammalian cells blocks the rapid effects of insulin. Proc. Natl. Acad. Sci. U. S. A. 84:41–5.CrossRefGoogle Scholar
  15. 15.
    Alghamdi F, et al. (2014) A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes. Cell Signal. 26:1355–68.CrossRefGoogle Scholar
  16. 16.
    Liu Y, et al. (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature. 456:269–73.CrossRefGoogle Scholar
  17. 17.
    Kim DH, et al. (2011) FoxO6 integrates insulin signaling with gluconeogenesis in the liver. Diabetes. 60:2763–74.CrossRefGoogle Scholar
  18. 18.
    Ceriello A. (2005) Acute hyperglycaemia: a ‘new’ risk factor during myocardial infarction. Eur. Heart J. 26:328–31.CrossRefGoogle Scholar
  19. 19.
    Opie LH. (2008) Metabolic management of acute myocardial infarction comes to the fore and extends beyond control of hyperglycemia. Circulation. 117:2172–7.CrossRefGoogle Scholar
  20. 20.
    Smit JW, Romijn JA. (2006) Acute insulin resistance in myocardial ischemia: causes and consequences. Semin. Cardiothorac. Vasc. Anesth. 10:215–9.CrossRefGoogle Scholar
  21. 21.
    Ma Y, et al. (2003) Hemorrhage induces the rapid development of hepatic insulin resistance. Am. J. Physiol. Gastrointest. Liver Physiol 284:G107–15.CrossRefGoogle Scholar
  22. 22.
    Carvalho LS, et al. (2012) High plasma HDL-C attenuates stress hyperglycemia during acute phase of myocardial infarction. Atherosclerosis 220:231–6.CrossRefGoogle Scholar
  23. 23.
    Thompson LH, et al. (2008) Acute, muscle-type specific insulin resistance following injury. Mol. Med. 14:715–23.CrossRefGoogle Scholar
  24. 24.
    Li L, Thompson LH, Zhao L, Messina JL. (2009) Tissue-specific difference in the molecular mechanisms for the development of acute insulin resistance after injury. Endocrinology. 150:24–32.CrossRefGoogle Scholar
  25. 25.
    Corathers SD, Falciglia M. (2011) The role of hyperglycemia in acute illness: supporting evidence and its limitations. Nutrition. 27:276–81.CrossRefGoogle Scholar
  26. 26.
    Giraud J, et al. (2007) Phosphorylation of Irs1 at SER-522 inhibits insulin signaling. Mol. Endocrinol. 21:2294–302.CrossRefGoogle Scholar
  27. 27.
    Hoehn KL, et al. (2008) IRS1-independent defects define major nodes of insulin resistance. Cell Metab. 7:421–33.CrossRefGoogle Scholar
  28. 28.
    Vasudevan AR, Balasubramanyam A. (2004) Thiazolidinediones: a review of their mechanisms of insulin sensitization, therapeutic potential, clinical efficacy, and tolerability. Diabetes Technol. Ther. 6:850–63.CrossRefGoogle Scholar
  29. 29.
    Jiang G, et al. (2002) Potentiation of insulin signaling in tissues of Zucker obese rats after acute and long-term treatment with PPARgamma agonists. Diabetes. 51:2412–9.CrossRefGoogle Scholar
  30. 30.
    Potenza MA, et al. (2006) Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. Diabetes. 55:3594–603.CrossRefGoogle Scholar
  31. 31.
    Singh S, Loke YK, Furberg CD. (2007) Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA. 298:1189–95.CrossRefGoogle Scholar
  32. 32.
    Home PD, et al. (2009) Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. 373:2125–35.CrossRefGoogle Scholar
  33. 33.
    Bach RG, et al. (2013) Rosiglitazone and outcomes for patients with diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Circulation. 128:785–94.CrossRefGoogle Scholar
  34. 34.
    Manning BD, Cantley LC. (2007) AKT/PKB signaling: navigating downstream. Cell. 129:1261–74.CrossRefGoogle Scholar
  35. 35.
    Vilahur G, et al. (2011) Molecular and cellular mechanisms involved in cardiac remodeling after acute myocardial infarction. J. Mol. Cell. Cardiol. 50:522–33.CrossRefGoogle Scholar
  36. 36.
    Ruparelia N, et al. (2013) Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus. Inflamm. Res. 62:515–25.CrossRefGoogle Scholar
  37. 37.
    Ronco C, et al. (2008) Cardiorenal syndrome. J. Am. Coll. Cardiol. 52:1527–39.CrossRefGoogle Scholar

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Authors and Affiliations

  • Jiali Wang
    • 1
    • 2
    • 3
    • 4
  • Baoshan Liu
    • 1
    • 2
    • 3
    • 4
  • Hui Han
    • 1
    • 2
  • Qiuhuan Yuan
    • 1
    • 3
    • 4
  • Mengyang Xue
    • 1
    • 3
    • 4
  • Feng Xu
    • 1
    • 2
    • 3
    • 4
  • Yuguo Chen
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Department of Emergency, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu HospitalShandong UniversityJinanChina
  2. 2.Chest Pain Center, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu HospitalShandong UniversityJinanChina
  3. 3.Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu HospitalShandong UniversityJinanChina
  4. 4.Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health Qilu HospitalShandong UniversityJinanChina
  5. 5.Qilu HospitalShandong UniversityJinanChina

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