Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes

Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes

Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2...

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Main Authors: Sevil Korkmaz-Icöz, Alice Lehner, Shiliang Li, Adrian Vater, Tamás Radovits, Péter Hegedűs, Mihály Ruppert, Paige Brlecic, Markus Zorn, Matthias Karck, Gábor Szabó
Format: Article
Language:English
Published: Hindawi Limited 2015-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2015/396414
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spelling doaj-77bb4dc71b784d93b193a11f89d6c2982020-11-24T22:47:30ZengHindawi LimitedJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/396414396414Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression ChangesSevil Korkmaz-Icöz0Alice Lehner1Shiliang Li2Adrian Vater3Tamás Radovits4Péter Hegedűs5Mihály Ruppert6Paige Brlecic7Markus Zorn8Matthias Karck9Gábor Szabó10Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyHeart and Vascular Center, Semmelweis University, 1122 Budapest, HungaryDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Internal Medicine I, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, GermanyDespite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2 diabetic Goto-Kakizaki (GK) rats (16-week-old) underwent 45 min occlusion of the left anterior descending coronary artery and 24 h reperfusion. The plasma glucose level was significantly higher in diabetic rats compared to the nondiabetics. Diabetes mellitus was associated with ventricular hypertrophy and increased interstitial fibrosis. Inducing myocardial infarction increased the glucose levels in diabetic compared to nondiabetic rats. Furthermore, the infarct size was smaller in GK rats than in the control group. Systolic and diastolic functions were impaired in W + MI and did not reach statistical significance in GK + MI animals compared to the corresponding controls. Among the 125 genes surveyed, 35 genes showed a significant change in expression in GK + MI compared to W + MI rats. Short-term diabetes promotes compensatory mechanisms that may provide cardioprotection against ischemia/reperfusion injury, at least in part, by increased antioxidants and the upregulation of the prosurvival PI3K/Akt pathway, by the downregulation of apoptotic genes, proinflammatory cytokine TNF-α, profibrogenic TGF-β, and hypertrophic marker α-actin-1.http://dx.doi.org/10.1155/2015/396414
collection DOAJ
language English
format Article
sources DOAJ
author Sevil Korkmaz-Icöz
Alice Lehner
Shiliang Li
Adrian Vater
Tamás Radovits
Péter Hegedűs
Mihály Ruppert
Paige Brlecic
Markus Zorn
Matthias Karck
Gábor Szabó
spellingShingle Sevil Korkmaz-Icöz
Alice Lehner
Shiliang Li
Adrian Vater
Tamás Radovits
Péter Hegedűs
Mihály Ruppert
Paige Brlecic
Markus Zorn
Matthias Karck
Gábor Szabó
Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes
Journal of Diabetes Research
author_facet Sevil Korkmaz-Icöz
Alice Lehner
Shiliang Li
Adrian Vater
Tamás Radovits
Péter Hegedűs
Mihály Ruppert
Paige Brlecic
Markus Zorn
Matthias Karck
Gábor Szabó
author_sort Sevil Korkmaz-Icöz
title Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes
title_short Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes
title_full Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes
title_fullStr Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes
title_full_unstemmed Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes
title_sort mild type 2 diabetes mellitus reduces the susceptibility of the heart to ischemia/reperfusion injury: identification of underlying gene expression changes
publisher Hindawi Limited
series Journal of Diabetes Research
issn 2314-6745
2314-6753
publishDate 2015-01-01
description Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2 diabetic Goto-Kakizaki (GK) rats (16-week-old) underwent 45 min occlusion of the left anterior descending coronary artery and 24 h reperfusion. The plasma glucose level was significantly higher in diabetic rats compared to the nondiabetics. Diabetes mellitus was associated with ventricular hypertrophy and increased interstitial fibrosis. Inducing myocardial infarction increased the glucose levels in diabetic compared to nondiabetic rats. Furthermore, the infarct size was smaller in GK rats than in the control group. Systolic and diastolic functions were impaired in W + MI and did not reach statistical significance in GK + MI animals compared to the corresponding controls. Among the 125 genes surveyed, 35 genes showed a significant change in expression in GK + MI compared to W + MI rats. Short-term diabetes promotes compensatory mechanisms that may provide cardioprotection against ischemia/reperfusion injury, at least in part, by increased antioxidants and the upregulation of the prosurvival PI3K/Akt pathway, by the downregulation of apoptotic genes, proinflammatory cytokine TNF-α, profibrogenic TGF-β, and hypertrophic marker α-actin-1.
url http://dx.doi.org/10.1155/2015/396414
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