ABSTRACT
The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/µl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1ß, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development.
Subject(s)
Diabetes Mellitus, Type 2/genetics , Hypertrophy, Left Ventricular/genetics , Myocardium/metabolism , Ventricular Dysfunction, Left/genetics , Ventricular Function, Left , Ventricular Pressure , Animals , Apoptosis/genetics , Atrial Natriuretic Factor/genetics , Blood Glucose/metabolism , C-Reactive Protein/genetics , Connective Tissue Growth Factor/genetics , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/physiopathology , Down-Regulation , Echocardiography , Electrocardiography , Fibrosis , Glucose Tolerance Test , Glycosuria , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Left Ventricular/physiopathology , Immunohistochemistry , In Situ Nick-End Labeling , Inflammation/genetics , Interleukin-1beta/genetics , Male , Myocardium/pathology , Natriuretic Peptide, Brain/metabolism , Oxidative Stress/genetics , Peptide Fragments/metabolism , Polymerase Chain Reaction , RNA, Messenger/metabolism , Rats , Rats, Wistar , Signal Transduction , Troponin T/metabolism , Tumor Necrosis Factor-alpha/genetics , Tyrosine/analogs & derivatives , Tyrosine/metabolism , Up-Regulation , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/physiopathologyABSTRACT
BACKGROUND: The East Asian mosquito species Aedes koreicus was recorded out of its native range for the first time in Belgium in 2008. Since then, several other European populations or single individuals have been observed throughout Europe with reports from Italy, Switzerland, European Russia, Slovenia, Germany and Hungary. The Italian population seems to be the only one that is expanding rapidly, so the Swiss population very likely derives from it. RESULTS: In a surveillance program for invasive mosquito species, a single larva of Ae. koreicus was found in a cemetery vase in 2016 in the city of Wiesbaden, Germany. In the following year the finding was confirmed and an established population could be proven over an area of about 50 km2. The morphological identification of the first larva was confirmed by sequencing of a region within the nad4 sequence. A study of adult females showed that the morphological characteristics of this population are not identical to the populations from Belgium and Italy. The eggs and larvae were found together with Aedes j. japonicus in the same breeding sites and ovitraps, as well as with other indigenous mosquito species such as Culex pipiens/Culex torrentium, Aedes geniculatus and Anopheles plumbeus. CONCLUSIONS: Since the newly discovered population in Germany shows different morphological characteristics to the populations in Belgium and Italy, it seems to originate from an independent introduction. It remains unknown how the introduction took place. A further spread similar to the one in northern Italy can be assumed for the future due to similar climatic conditions.
Subject(s)
Aedes/anatomy & histology , Aedes/genetics , Aedes/physiology , Animal Distribution , Animals , Europe , Female , Germany , Larva/anatomy & histology , Larva/genetics , Larva/physiology , MaleABSTRACT
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-ß, and hypertrophic marker α-actin-1.
Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Cardiomyopathies/metabolism , Gene Expression Regulation , Muscle Proteins/metabolism , Myocardial Infarction/complications , Myocardial Reperfusion Injury/metabolism , Myocardium/metabolism , Animals , Blood Glucose/analysis , Cardiomegaly/etiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Diabetic Cardiomyopathies/pathology , Diabetic Cardiomyopathies/physiopathology , Disease Susceptibility , Fibrosis , Gene Expression Profiling , Heart/physiopathology , Male , Muscle Proteins/genetics , Myocardial Infarction/blood , Myocardial Infarction/physiopathology , Myocardial Ischemia/complications , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/complications , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardium/pathology , Random Allocation , Rats, Inbred Strains , Rats, Wistar , Severity of Illness IndexABSTRACT
AIMS: Myocardial infarction (MI) is a common cause of mortality in patients with diabetes mellitus (DM) and vascular dysfunction is a major component of diabetic cardiomyopathy. We investigated the systemic influence of acute MI on the diabetes-induced pathogenic changes in the rat aorta. METHODS: Nondiabetic Wistar (W) and type-2 diabetic Goto-Kakizaki (GK) rats underwent 45min of left anterior descending coronary artery occlusion followed by 24h of reperfusion. Isometric force was measured using organ bath. RESULTS: Plasma glucose-levels were significantly higher in diabetic rats (GK+sham: 13±2mM; GK+MI: 19±2mM) compared to nondiabetic rats (W+sham: 8±0mM; W+MI: 8±1mM). Acetylcholine-induced relaxation was significantly weaker in rings from W+MI and GK+MI rats compared to corresponding sham-operated animals. Myocardial reperfusion injury was smaller in GK+MI than W+MI rats, and the concentration-response curves to acetylcholine were significantly enhanced in rings from GK+MI than W+MI rats. Nevertheless, the relaxation response to acetylcholine was similar in W+sham and GK+sham. Densitometric analysis of bands for endothelial nitric oxide synthase showed a significant decrease in W+MI rats compared to W+sham and GK+sham animals. Aortas from both GK+sham and GK+MI rats showed impaired contractile responses to phenylephrine in comparison with the nondiabetics. CONCLUSIONS: For the first time we showed that short-term and mild type-2 DM improved remote endothelial dysfunction after reperfused acute MI.