Effect of Diabetes Mellitus and Its Control on Myocardial Contractile Function in Rats

Authors

  • Bassem M. Alsawy Department of Physiology, Faculty of Medicine, Beni Swaif University, Cairo
  • Magdi A. El-Damarawi Department of Physiology, Faculty of Medicine, Tanta University, Tanta

DOI:

https://doi.org/10.3889/oamjms.2014.074

Keywords:

Diabetes mellitus, Thyroid dysfunction, Diabetic cardiomyopathy, Insulin, Rosiglitazone

Abstract

AIM: This work was done to study the effect of both types of diabetes mellitus (DM) on myocardial contractility in rats. Also, we investigated the role of treatment of DM with insulin and rosiglitazone (used as treatment for type 1 and type 2 DM respectively) in improvement of myocardial dysfunction in diabetic rats.

METHODS: The study included 50 male Wistar albino rats, divided into 5 groups: control (group I), streptozotocin induced type 1 DM (group II), fructose induced type 2 DM (group III), insulin treated type 1 diabetic rats (group IV) and rosiglitazone treated type 2 diabetic rats (group V). At the end of the study, retro-orbital blood samples were withdrawn and blood glucose, plasma triglyceride (TG), total cholesterol (TC) and thyroid hormones levels were measured. Rats were then anesthetized and their hearts were excised and connected to Langendorff apparatus to perform mechanical cardiac performance tests including heart rate (HR), left ventricular developed pressure (LVDP) and maximum rate of pressure rise (+dp/dt).

RESULTS: Data of the study showed that relative to control group, there was significant increase in blood glucose, plasma TG and TC levels while, thyroid hormones and myocardial performance parameters showed significant decrease in both type 1 and type 2 diabetic rats. Treatment of type 1 diabetic rats with insulin and type 2 with rosiglitazone resulted in significant decrease in blood glucose, plasma TG and TC levels associated with significant improvement in thyroid hormones and myocardial performance parameters. The results also showed that insulin treatment of type 1 was more effective in ameliorating all parameters than treatment of type 2 by rosiglitazone.

CONCLUSION: We concluded that the induction of both types of diabetes resulted in decreased myocardial performance parameters. The  treatment of type 1 and type 2 diabetes by insulin and oral rosiglitazone respectively improved to a great extent the altered metabolism and  mechanical myocardial parameters, with more improving effect of  insulin in type 1 than rosiglitazone in type 2 DM.

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References

Wu CJ, Sung HC, Chang AM, Atherton J, Kostner K, Courtney M, McPhail SM. Protocol for a randomised blocked design study using telephone and text-messaging to support cardiac patients with diabetes: a cross cultural international collaborative project. BMC Health Serv Res. 2013; 13:402. DOI: https://doi.org/10.1186/1472-6963-13-402

Bugger H, Abel ED. Rodent models of diabetic cardiomyopathy. Disease Models & Mechanisms. 2009; 2:454-466. DOI: https://doi.org/10.1242/dmm.001941

Belke DD, Larsen TS, Gibbs EM, Sevenson DL. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic mice. Am J Physiol Endocrinol Metab. 2004; 279:1104-13. DOI: https://doi.org/10.1152/ajpendo.2000.279.5.E1104

Sunderesan PR, Sharma VK, Gingold SL. Decreased beta adrenergic receptors in rat heart in streptozotocin induced diabetes: Role of thyroid hormones. Endocrinol. 1984; 114:1358–1363. DOI: https://doi.org/10.1210/endo-114-4-1358

Hirayama H, Sugano M, Abe N, Yonemoch H, Makino N. Torglitazone an antidiabetic drug improves left ventricular mass and diastolic function in normotensive diabetic patients. Int J Cardiol. 2006; 77:75-9. DOI: https://doi.org/10.1016/S0167-5273(00)00411-3

Falzacappa CV, Mangialardo C, Madaro L, Ranieri D, Lupoi L, Stigliano A, Torrisi MR, Bouché M, Toscano V, Misiti S. Thyroid hormone T3 counteracts STZ induced diabetes in mouse. Plos One. 2011; 6 (5):e19839. DOI: https://doi.org/10.1371/journal.pone.0019839

Peppa M, Betsi G, Dimitriadis G. Lipid abnormalities and cardiometabolic risk in patients with overt and subclinical thyroid disease. J Lipids. 2011;2011:575840. DOI: https://doi.org/10.1155/2011/575840

Keshor M, Takanda J, Roterto L. Ischemic heart disease: diabetes and vascular risk. Am J Cardiol. 2004; 4: 254-315.

Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat. A model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005; 52:313 – 320. DOI: https://doi.org/10.1016/j.phrs.2005.05.004

Huang BW, Chiang MT, Yao HT, Chiang W. The effect of high-fat and high-fructose diets on glucose tolerance and plasma lipid and leptin levels in rats. Diabetes Obes Metab. 2004; 6(2):120-6. DOI: https://doi.org/10.1111/j.1462-8902.2004.00323.x

Zhang L, Parratt JR, Beastall GH, Pyne NJ, Furman BL. Streptozotocin diabetes protects against arrhythmias in rat isolated heart, role of hypothyroidism. Eur J Pharmacol. 2002; 25:43-269. DOI: https://doi.org/10.1016/S0014-2999(01)01398-X

Takazawa T, Yamauchi T, Tsuchida A, Takata M, Hada Y, Iwabu M, Okada-Iwabu M, Ueki K, Kadowaki T. Peroxisome Proliferator-activated Receptor ï§Agonist Rosiglitazone Increases Expression of Very Low Density Lipoprotein Receptor Gene in Adipocytes. J Biol Chem. 2009; 284:30049-30057. DOI: https://doi.org/10.1074/jbc.M109.047993

Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem. 1969; 6:24. DOI: https://doi.org/10.1177/000456326900600108

Wahlefeld AW. Triglyceride determination after enzymatic hydrolysis. In Methods of Enzymatic Analysis (Bermeyer,H.U.,Eds.), Academic press, New York, 1974: pp. 18-31. DOI: https://doi.org/10.1016/B978-0-12-091304-6.50036-7

Sundvall J, Leiviskä J, Alfthan G, Vartiainen E. Serum cholesterol during 27 years: assessment of systematic error and affecting factors and their role in interpreting population trends. Clin Chim Acta. 2007; 378(1-2):93-8. DOI: https://doi.org/10.1016/j.cca.2006.10.021

Burtis CA, Ashwood ER (Eds.). Tietz textbook of clinical chemistry. 2nd ed., Philadelphia: W. B. Saunders Company, 1994: pp. 1711–1715.

Joffe II, Travers KE, Perreault-Micale CL, et al. Abnormal cardiac function in the streptozotocin-induced, non–insulin dependent diabetic rat. J Am Coll Cardiol. 1999; 34(7):2111- 2119. DOI: https://doi.org/10.1016/S0735-1097(99)00436-2

Dansky H, McClain DA, McIndoe R, Wassef MK, Rabadan-Diehl C, Goldberg IJ. Recipes for Creating Animal Models of Diabetic Cardiovascular Disease. Circ Res. 2007; 100: 1415-1427. DOI: https://doi.org/10.1161/01.RES.0000266449.37396.1f

Chaudhuri A, Dandona P. Effects of insulin and other antihyperglycaemic agents on lipid profiles of patients with diabetes. Diabetes Obes Metab. 2011; 13(10):869-79. DOI: https://doi.org/10.1111/j.1463-1326.2011.01423.x

Després JP, Marette A. Relation of components of insulin resistance syndrome to coronary disease risk. Curr Opin Lipidol. 2001, 5:274-289. DOI: https://doi.org/10.1097/00041433-199408000-00006

Virmani R, Burke AP, Kolodgie F. Morphological characteristics of coronary atherosclerosis in diabetes mellitus. Can J Cardiol. 2007; 22(Suppl B):81B–84B. DOI: https://doi.org/10.1016/S0828-282X(06)70991-6

Steger RW, Rabe MB. The effect of diabetes mellitus on endocrine and reproductive function. Proc Soc Exp Biol Med. 1997; 214(1):1-11. DOI: https://doi.org/10.3181/00379727-214-44064

Duntas LH, Orgiazzi J, Brabant G. The Interface Between Thyroid and Diabetes Mellitus. Clin Endocrinol. 2011; 75(1):1-9. DOI: https://doi.org/10.1111/j.1365-2265.2011.04029.x

Lorenzo O, Ramírez E, Picatoste B, Egido J, Tuñón J. Alteration of energy substrates and ROS production in diabetic cardiomyopathy. Mediators Inflamm. 2013;2013:461967. DOI: https://doi.org/10.1155/2013/461967

Bayeva M, Sawicki KT, Ardehali H. Taking Diabetes to Heart−Deregulation of Myocardial Lipid Metabolism in Diabetic Cardiomyopathy. J Am Heart Assoc. 2013; 2:e000433. DOI: https://doi.org/10.1161/JAHA.113.000433

Carley AN, Severson DL. Fatty acid metabolism is enhanced in type 2 diabetic hearts. Biochim Biophys Acta. 2005; 1734(2):112-126. DOI: https://doi.org/10.1016/j.bbalip.2005.03.005

Asrih M, Steffens S. Emerging role of epigenetics and mRNA in diabetic cardiomyopathy. Cardiovascular Pathology. 2013; 22:117–125. DOI: https://doi.org/10.1016/j.carpath.2012.07.004

Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005; 54(6):1615–1625. DOI: https://doi.org/10.2337/diabetes.54.6.1615

Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006; 114(6):597–605. DOI: https://doi.org/10.1161/CIRCULATIONAHA.106.621854

Braz JC, Gregory K, Pathak A et al. PKC-α regulates cardiac contractility and propensity toward heart failure. Nature Medicine. 2004; 10(3):248–254. DOI: https://doi.org/10.1038/nm1000

Coughlan MT, Thorburn DR, Penfold SA et al. Rage-induced cytosolic ROS promote mitochondrial superoxide generation in diabetes. J Am Soc Nephrol. 2009; 20(4):742–752. DOI: https://doi.org/10.1681/ASN.2008050514

Ceriello A. Acute hyperglycaemia: a new risk factor during myocardial infarction. Eur Heart J. 2005; 26(4):328–331. DOI: https://doi.org/10.1093/eurheartj/ehi049

Sykiotis GP, Papavassiliou AG. Serine phosphorylation of insulin receptor substrate-1: a novel target for the reversal of insulin resistance. Mol Endocrinol. 2001; 15:1864–1869. DOI: https://doi.org/10.1210/mend.15.11.0725

Huang TH, Yang Q, Harada M, Uberai J, Radford J, Li GQ, Yamahara J, Roufogalis BD, Li Y. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: modulation of cardiac PPAR-alpha-mediated transcription of fatty acid metabolic genes. Toxicol Appl Pharmacol. 2006; 210:78–85. DOI: https://doi.org/10.1016/j.taap.2005.07.020

Van Herpen NA, Schrauwen-Hinderling VB. Lipid accumulation in non adipose tissue and lipotoxicity. Physiol Behav. 2008; 94:231–241. DOI: https://doi.org/10.1016/j.physbeh.2007.11.049

Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, Nadal-Ginard B, Anversa P. Myocardial cell death in human diabetes. Circ Res. 2000; 87:1123–1132. DOI: https://doi.org/10.1161/01.RES.87.12.1123

Wu QD, Wang JH, Fennessy F, Redmond HP, Bouchier-Hayes D. Taurine prevents high-glucose-induced human vascular endothelial cell apoptosis. Am J Physiol. 1999; 277:C1229–38. DOI: https://doi.org/10.1152/ajpcell.1999.277.6.C1229

Zhao XY, Hu SJ, Li J, Mou Y, Chen BP, Xia Q. Decreased cardiac sarcoplasmic reticulum Ca2+ -ATPase activity contributes to cardiac dysfunction in streptozotocin-induced diabetic rats. J Physiol Biochem. 2006;62(1):1-8. DOI: https://doi.org/10.1007/BF03165800

Bers DM. Cardiac excitation-contraction coupling. Nature. 2002; 415 :198 –205. DOI: https://doi.org/10.1038/415198a

Kaidar A, Marx M, Lubec B, Lubec G. L-arginine reduces heart collagen accumulation in the diabetic db/db mouse. Circulation. 2007; 90:479 –483. DOI: https://doi.org/10.1161/01.CIR.90.1.479

Ilic S, Tadic M, Ivanovic B, Caparevic Z, Trbojevic B, Celic V. Left and right ventricular structure and function in subclinical hypothyroidism: The effects of one-year levothyroxine treatment. Med Sci Monit. 2013;10:19:960-8. DOI: https://doi.org/10.12659/MSM.889621

Rudski LG, Lai WW, Afilalo J et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010; 23(7):685–713.

Aksoy D, Cinar N, Harmanci A et al. Serum resistin and high sensitive CRP levels in patients with subclinical hypothyroidism before and after L-thyroxine therapy. Med Sci Monit. 2013; 19:210–15. DOI: https://doi.org/10.12659/MSM.883847

Brenta G, Mutti LA, Schnitman M et al. Assessment of left ventricular diastolic function by radionuclide ventriculography at rest and exercise in subclinical hypothyroidism, and its response to L-thyroxine therapy. Am J Cardiol. 2003; 91(11):1327–30. DOI: https://doi.org/10.1016/S0002-9149(03)00322-9

Biondi B, Palmieri EA, Lombardi G, Fazio S. Subclinical hypothyroidism and cardiac function. Thyroid. 2002; 12(6):505–10. DOI: https://doi.org/10.1089/105072502760143890

Jagdish A, Singh H, Batra A et al. An echocardiographic study on the effect of levothyroxine therapy on cardiac function and structure in hypothyroidism. JIACM. 2009; 10(1–2):27–31.

Fommei E, Iervasi G. The role of thyroid hormone in blood pressure homeostasis: evidence from short-term hypothyroidism in humans. J Clin Endocrinol Metab. 2002; 87(5):1996–2000. DOI: https://doi.org/10.1210/jcem.87.5.8464

Van den Bergh A, Flameng W, Herijgers P. Type II diabetic mice exhibit contractile dysfunction but maintain cardiac output by favourable loading conditions. Eur J Heart Fail. 2006; 8(8):777-783. DOI: https://doi.org/10.1016/j.ejheart.2006.03.001

Kosova F, Sepici-Dincel A, Engin A, MemiÅŸ L, Koca C,mAltan N. The thyroid hormone mediated effects of insulin on serum leptin levels of diabetic rats. Endocrine. 2008; 317:22. DOI: https://doi.org/10.1007/s12020-008-9093-7

Sathish R, Mohan V. Diabetes and thyroid disease – A review. Int J Diabetes Dev Ctries. 2003; 23:120-3.

Jie YU, Hai-feng ZHANG, Feng WU, Qiu-xia LI, Heng MA, Wen-yi GUO, Hai-chang WANG, Feng GAO. Insulin improves cardiomyocyte contractile function through enhancement of SERCA2a activity in simulated ischemia/reperfusion. Acta Pharmacol Sin. 2006; 27(7): 919–926. DOI: https://doi.org/10.1111/j.1745-7254.2006.00388.x

Kim HW, Ch YS, Lee HR, Park SY, Kim YH. Diabetic alterations in cardiac sarcoplasmic reticulum Ca2+-ATPase and phospholamban protein expression. Life Sci. 2003; 70 :367–379. DOI: https://doi.org/10.1016/S0024-3205(01)01483-7

Bidasee KR, Nallani K, Henry B, Dincer UD, Besch HR J.r. Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts. Mol Cell Biochem. 2013; 249(1-2):113-23. DOI: https://doi.org/10.1007/978-1-4419-9236-9_15

Zhang B, Roth RA. A region of the insulin receptor important for ligand binding (residues 450-601) is recognized by patients autoimmune antibodies and inhibitory monoclonal antibodies. Proc Natl Acad Sci. 2006; 88:9858-9862. DOI: https://doi.org/10.1073/pnas.88.21.9858

Jeschke MG, Klein D, Bolder U, Einspanier R. Insulin attenuates the systemic inflammatory response in endotoxemic rats. Endocrinology. 2004; 145: 4084–93. DOI: https://doi.org/10.1210/en.2004-0592

Belke DD, Swanson EA, Dillmann WH. Decreased Sarcoplasmic Reticulum Activity and Contractility in Diabetic db/db Mouse Heart. Diabetes. 2004; 53:3201-3208. DOI: https://doi.org/10.2337/diabetes.53.12.3201

Shah SC, Malone JI, Simpson NE. A randomized trial of intensive insulin therapy in newly diagnosed type I insulin-dependent diabetes mellitus. N Engl J Med. 2006; 320:550-554. DOI: https://doi.org/10.1056/NEJM198903023200902

Inukai K. P85α gene generates three isoforms of regulatory subunit for phosphatidylinostol-3 kinase (PI3-kinase) p50α, with different PI3-kinase activity elevating responses to insulin. J Biol Chem. 2005; 272:7873-7882. DOI: https://doi.org/10.1074/jbc.272.12.7873

Artie AD. Insig: a significant integrator of nutrient and hormonal signals. J Clin Invest. 2004; 113:1112–1114. DOI: https://doi.org/10.1172/JCI21450

Carpino N. P62 dok: a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells. Cell. 2005; 88:197-204. DOI: https://doi.org/10.1016/S0092-8674(00)81840-1

Krook A, O'Rahilly S. Mutant insulin receptors in syndromes of insulin resistance (review). Endocr Metab. 2006; 10:97-122. DOI: https://doi.org/10.1016/S0950-351X(96)80330-2

Ovalle F, Bell DSH. Effect of Rosiglitazone Versus Insulin on the Pancreatic _-Cell Function of Subjects With Type 2 Diabetes. Diabetes Care. 2004; 27(11):2585-2589. DOI: https://doi.org/10.2337/diacare.27.11.2585

Kumar J, Liebel R. To eat or not to eat-how the gut talks to the brain. NEJM. 2004; 349:926-928. DOI: https://doi.org/10.1056/NEJMp038114

Sahin M, Tutuncu NB, Ertugrul D, Tanaci M, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B 12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007; 21(2):118-23. DOI: https://doi.org/10.1016/j.jdiacomp.2005.10.005

Tepmongkol S, Keelawat S, Honsawek S, Ruangvejvorachai P. Rosiglitazone Effect on Radioiodine Uptake in Thyroid Carcinoma Patients with High Thyroglobulin but Negative Total Body Scan: A Correlation with the Expression of Peroxisome Proliferator–Activated Receptor-Gamma. Thyroid. 2008; 18(7):697-704. DOI: https://doi.org/10.1089/thy.2008.0056

Rillema JA, Williams CH, Moulden J, Golden KL. Effect of insulin on iodide uptake in mouse mammary gland explants. Exp Biol Med. (Maywood). 2002; 227(1):32-5. DOI: https://doi.org/10.1177/153537020222700106

Dong MJ, Akinari T, Hayato N, Ken-Ichiro F, Toshiharu A. Troglitazone prevents and reverses dyslipidemia, insulin secretory defects, and histologic abnormalities in a rat model of naturally occurring obese diabetes. Metab. 2006; 49:1167-1175. DOI: https://doi.org/10.1053/meta.2000.8599

Yang B, Li D, Phillips MI, Mehta P, Mehta JL. Myocardial angiotensin II receptor expression and ischemia-reperfusion injury. Vasc Med. 2005; 3:121–130. DOI: https://doi.org/10.1177/1358836X9800300206

Diep QN, El Mabrouk M, Cohn JS, Endemann D, Amiri F, Virdis A, Neves MF, Schiffrin EL. Structure, endothelial function, cell growth, and inflammation in blood vessels of angiotensin II-infused rats: role of peroxisome proliferator-activated receptor- . Circulation. 2007; 105:2296–2302. DOI: https://doi.org/10.1161/01.CIR.0000016049.86468.23

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2014-09-15

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1.
Alsawy BM, El-Damarawi MA. Effect of Diabetes Mellitus and Its Control on Myocardial Contractile Function in Rats. Open Access Maced J Med Sci [Internet]. 2014 Sep. 15 [cited 2024 May 9];2(3):431-8. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2014.074

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