title: Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes.
abstract: 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.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Sevil
authors.initials: S
authors.lastname: Korkmaz-Icöz
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Lehner
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Adrian
authors.initials: A
authors.lastname: Vater
authors.affiliation: Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany ; Heart and Vascular Center, Semmelweis University, 1122 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Hegedűs
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Mihály
authors.initials: M
authors.lastname: Ruppert
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Paige
authors.initials: P
authors.lastname: Brlecic
authors.affiliation: Department of Internal Medicine I, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Zorn
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D006332:Cardiomegaly / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004198:Disease Susceptibility; D005355:Fibrosis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose; D009124:Muscle Proteins