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Published in: Cardiovascular Diabetology 1/2015

Open Access 01-12-2015 | Original investigation

Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling

Authors: Christiane Malfitano, Alcione Lescano de Souza Junior, Mariana Carbonaro, Andressa Bolsoni-Lopes, Diego Figueroa, Leandro Ezequiel de Souza, Kleiton Augusto Santos Silva, Fernanda Consolim-Colombo, Rui Curi, Maria Claudia Irigoyen

Published in: Cardiovascular Diabetology | Issue 1/2015

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Abstract

Background

The effects of streptozotocin (STZ)-induced diabetes on heart metabolism and function after myocardial infarction (MI) remodelling were investigated in rats.

Methods

Fifteen days after STZ (50 mg/kg b.w. i.v.) injection, MI was induced by surgical occlusion of the left coronary artery. Two weeks after MI induction, contents of glycogen, ATP, free fatty acids and triacylglycerols (TG) and enzyme activities of glycolysis and Krebs cycle (hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase, citrate synthase) and expression of carnitine palmitoyl-CoA transferase I (a key enzyme of mitochondrial fatty acid oxidation) were measured in the left ventricle (LV). Plasma glucose, free fatty acids and triacylglycerol levels were determined. Ejection fraction (EF) and shortening fraction (SF) were also measured by echocardiography.

Results

Glycogen and TG contents were increased (p < 0.05) whereas ATP content was decreased in the LV of the non-infarcted diabetic group when compared to the control group (p < 0.05). When compared to infarcted control rats (MI), the diabetic infarcted rats (DI) showed (p < 0.05): increased plasma glucose and TG levels, elevated free fatty acid levels and increased activity of, citrate synthase and decreased ATP levels in the LV. Infarct size was smaller in the DI group when compared to MI rats (p < 0.05), and this was associated with higher EF and SF (p < 0.05).

Conclusions

Systolic function was preserved or recovered more efficiently in the heart from diabetic rats two weeks after MI, possibly due to the high provision of glucose and free fatty acids from both plasma and heart glycogen and triacylglycerol stores.
Literature
2.
go back to reference Ravingerova T, Neckar J, Kolar F. Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes. Mol Cell Biochem. 2003;249:167–74.CrossRefPubMed Ravingerova T, Neckar J, Kolar F. Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes. Mol Cell Biochem. 2003;249:167–74.CrossRefPubMed
4.
go back to reference Ravingerova T, Neckar J, Kolar F, Stetka R, Volkovova K, Ziegelhöffer A, et al. Ventricular arrhythmias following coronary artery occlusion in rats: is the diabetic heart less or more sensitive to ischaemia? Basic Res Cardiol. 2001;96:160–8. doi:10.1007/s003950170066.CrossRefPubMed Ravingerova T, Neckar J, Kolar F, Stetka R, Volkovova K, Ziegelhöffer A, et al. Ventricular arrhythmias following coronary artery occlusion in rats: is the diabetic heart less or more sensitive to ischaemia? Basic Res Cardiol. 2001;96:160–8. doi:10.​1007/​s003950170066.CrossRefPubMed
5.
go back to reference Bäcklund T, Palojoki E, Saraste A, Eriksson A, Finckenberg P, Kytö V, et al. Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes. Diabetologia. 2004;47:325–30. doi:10.1007/s00125-003-1311-5.CrossRefPubMed Bäcklund T, Palojoki E, Saraste A, Eriksson A, Finckenberg P, Kytö V, et al. Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes. Diabetologia. 2004;47:325–30. doi:10.​1007/​s00125-003-1311-5.CrossRefPubMed
7.
go back to reference Malfitano C, lba Loureiro TC, Rodrigues B, Sirvente R, Salemi VM, Rabechi NB, et al. Hyperglycaemia protects the heart after myocardial infarction: aspects of programmed cell survival and cell death. Eur J Heart Fail. 2010;12:659–67. doi:10.1093/eurjhf/hfq053.CrossRefPubMed Malfitano C, lba Loureiro TC, Rodrigues B, Sirvente R, Salemi VM, Rabechi NB, et al. Hyperglycaemia protects the heart after myocardial infarction: aspects of programmed cell survival and cell death. Eur J Heart Fail. 2010;12:659–67. doi:10.​1093/​eurjhf/​hfq053.CrossRefPubMed
12.
go back to reference Ravingerova T, Stetka R, Volkovova K, Pancza D, Dzurba A, Ziegelhöffer A, et al. Acute diabetes modulates response to ischemia in isolated rat heart. Mol Cell Biochem. 2000;210(1–2):143–51.CrossRefPubMed Ravingerova T, Stetka R, Volkovova K, Pancza D, Dzurba A, Ziegelhöffer A, et al. Acute diabetes modulates response to ischemia in isolated rat heart. Mol Cell Biochem. 2000;210(1–2):143–51.CrossRefPubMed
14.
go back to reference Rochetaing A, Kreher P. Reactive hyperemia during early reperfusion as a determinant of improved functional recovery in ischemic preconditioned rat hearts. J Thorac Cardiovasc Surg. 2003;125(6):1516–25.CrossRefPubMed Rochetaing A, Kreher P. Reactive hyperemia during early reperfusion as a determinant of improved functional recovery in ischemic preconditioned rat hearts. J Thorac Cardiovasc Surg. 2003;125(6):1516–25.CrossRefPubMed
16.
go back to reference Gamble J, Lopaschuk GD. Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats. Biochim Biophys Acta. 1994;1225(2):191–9.CrossRefPubMed Gamble J, Lopaschuk GD. Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats. Biochim Biophys Acta. 1994;1225(2):191–9.CrossRefPubMed
21.
go back to reference Akhtar MS, Pillai KK, Hassan Q, Ansari SH, Ali J, Akhtar M, et al. Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy. Clin Exp Hypertens. 2015;24:1–13. Akhtar MS, Pillai KK, Hassan Q, Ansari SH, Ali J, Akhtar M, et al. Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy. Clin Exp Hypertens. 2015;24:1–13.
24.
25.
26.
go back to reference Decker K, Keppler D. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol. 1974;71:77–106.PubMed Decker K, Keppler D. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol. 1974;71:77–106.PubMed
27.
go back to reference Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed
28.
go back to reference Crabtree B, Newsholme EA. The activities of phosphorylase, hexokinase, phosphofructokinase, lactate dehydrogenase and the glycerol 3-phosphate dehydrogenases in muscles from vertebrates and invertebrates. Biochem J. 1972;126(1):49–58.PubMedCentralCrossRefPubMed Crabtree B, Newsholme EA. The activities of phosphorylase, hexokinase, phosphofructokinase, lactate dehydrogenase and the glycerol 3-phosphate dehydrogenases in muscles from vertebrates and invertebrates. Biochem J. 1972;126(1):49–58.PubMedCentralCrossRefPubMed
30.
go back to reference Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.CrossRefPubMed Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–5.CrossRefPubMed
31.
go back to reference Laybutt DR, Thompson AL, Cooney GJ, Kraegen EW. Selective chronic regulation of GLUT1 and GLUT4 content by insulin, glucose, and lipid in rat cardiac muscle in vivo. Am J Physiol. 1997;273:H1309–16.PubMed Laybutt DR, Thompson AL, Cooney GJ, Kraegen EW. Selective chronic regulation of GLUT1 and GLUT4 content by insulin, glucose, and lipid in rat cardiac muscle in vivo. Am J Physiol. 1997;273:H1309–16.PubMed
32.
go back to reference Ji XB, Li XR, Hao-Ding Sun Q, Zhou Y, Wen P, et al. Inhibition of uncoupling protein 2 attenuates cardiac hypertrophy induced by transverse aortic constriction in mice. Cell Physiol Biochem. 2015;36:1688–98. doi:10.1159/000430142.CrossRefPubMed Ji XB, Li XR, Hao-Ding Sun Q, Zhou Y, Wen P, et al. Inhibition of uncoupling protein 2 attenuates cardiac hypertrophy induced by transverse aortic constriction in mice. Cell Physiol Biochem. 2015;36:1688–98. doi:10.​1159/​000430142.CrossRefPubMed
33.
go back to reference Naserzadeh P, Hosseini MJ, MohamadzadehAsl B, Pourahmad J. Toxicity mechanisms of cigarette smoke on mouse fetus mitochondria. Iran J Pharm Res. 2015;14(Suppl):131–8.PubMedCentralPubMed Naserzadeh P, Hosseini MJ, MohamadzadehAsl B, Pourahmad J. Toxicity mechanisms of cigarette smoke on mouse fetus mitochondria. Iran J Pharm Res. 2015;14(Suppl):131–8.PubMedCentralPubMed
35.
go back to reference Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1:785–9.CrossRefPubMed Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963;1:785–9.CrossRefPubMed
37.
go back to reference Hirabara SM, Curi R, Maechler P. Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. J Cell Physiol. 2010;222(1):187–94. doi:10.1002/jcp.21936.CrossRefPubMed Hirabara SM, Curi R, Maechler P. Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. J Cell Physiol. 2010;222(1):187–94. doi:10.​1002/​jcp.​21936.CrossRefPubMed
39.
go back to reference Kokubun E, Hirabara SM, Fiamoncini J, Curi R, Haebisch H. Changes of glycogen content in liver, skeletal muscle, and heart from fasted rats. Cell Biochem Funct. 2009;27(7):488–95. doi:10.1002/cbf.1602.CrossRefPubMed Kokubun E, Hirabara SM, Fiamoncini J, Curi R, Haebisch H. Changes of glycogen content in liver, skeletal muscle, and heart from fasted rats. Cell Biochem Funct. 2009;27(7):488–95. doi:10.​1002/​cbf.​1602.CrossRefPubMed
41.
go back to reference Egorova MV, Afanas’ev SA, Popov SV, Karpov RS. Manifestation of adaptive changes during combined development of postinfarction remodeling of the heart and diabetes mellitus. Bull Exp Biol Med. 2010;150(2):172–4.CrossRefPubMed Egorova MV, Afanas’ev SA, Popov SV, Karpov RS. Manifestation of adaptive changes during combined development of postinfarction remodeling of the heart and diabetes mellitus. Bull Exp Biol Med. 2010;150(2):172–4.CrossRefPubMed
42.
go back to reference Masoud WG, Ussher JR, Wang W, Jaswal JS, Wagg CS, Dyck JR, et al. Failing mouse hearts utilize energy inefficiently and benefit from improved coupling of glycolysis and glucose oxidation. Cardiovasc Res. 2014;101(1):30–8. doi:10.1093/cvr/cvt216.CrossRefPubMed Masoud WG, Ussher JR, Wang W, Jaswal JS, Wagg CS, Dyck JR, et al. Failing mouse hearts utilize energy inefficiently and benefit from improved coupling of glycolysis and glucose oxidation. Cardiovasc Res. 2014;101(1):30–8. doi:10.​1093/​cvr/​cvt216.CrossRefPubMed
44.
go back to reference Duerr GD, Heinemann JC, Arnoldi V, Feisst A, Kley J, Ghanem A, et al. Cardiomyocyte specific peroxisome proliferator-activated receptor-α overexpression leads to irreversible damage in ischemic murine heart. Life Sci. 2014;102(2):88–97. doi:10.1016/j.lfs.2014.03.019.CrossRefPubMed Duerr GD, Heinemann JC, Arnoldi V, Feisst A, Kley J, Ghanem A, et al. Cardiomyocyte specific peroxisome proliferator-activated receptor-α overexpression leads to irreversible damage in ischemic murine heart. Life Sci. 2014;102(2):88–97. doi:10.​1016/​j.​lfs.​2014.​03.​019.CrossRefPubMed
47.
go back to reference Lung TW, Petrie D, Herman WH, Palmer AJ, Svensson AM, Eliasson B, et al. Severe hypoglycemia and mortality after cardiovascular events for type 1 diabetic patients in Sweden. Diabetes Care. 2014;37(11):2974–81. doi:10.2337/dc14-0405.CrossRefPubMed Lung TW, Petrie D, Herman WH, Palmer AJ, Svensson AM, Eliasson B, et al. Severe hypoglycemia and mortality after cardiovascular events for type 1 diabetic patients in Sweden. Diabetes Care. 2014;37(11):2974–81. doi:10.​2337/​dc14-0405.CrossRefPubMed
49.
go back to reference Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Wetterslev J. WITHDRAWN: targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2015;7:CD008143.PubMed Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal TP, Wetterslev J. WITHDRAWN: targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2015;7:CD008143.PubMed
Metadata
Title
Glucose and fatty acid metabolism in infarcted heart from streptozotocin-induced diabetic rats after 2 weeks of tissue remodeling
Authors
Christiane Malfitano
Alcione Lescano de Souza Junior
Mariana Carbonaro
Andressa Bolsoni-Lopes
Diego Figueroa
Leandro Ezequiel de Souza
Kleiton Augusto Santos Silva
Fernanda Consolim-Colombo
Rui Curi
Maria Claudia Irigoyen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2015
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-015-0308-y

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