effect of atorvastatin therapy in the adiponectin levels in an animal model of diabetes and...

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eccentric cardiac remodelling, but had no direct effect on glycaemic control. However the increased adiponectin levels potentially indicate improved insulin signalling. Keywords: Type II diabetes and obesity; Oxidative stress; Resistance training doi:10.1016/j.yjmcc.2007.03.775 Effect of atorvastatin therapy in the adiponectin levels in an animal model of diabetes and hypercaloric diet Pedro Monteiro, Paulo Matafome, Marta Paiva, Raquel Carreira, Raquel Seiça, Lino Gonçalves, Luís A. Providencia. Basic Research Unit in Cardiology, Cardiology Department and Physiology Department, Coimbra Medical School, Coimbra, Portugal Introduction: Obese diabetics have more and worse ischemic heart disease. It was already demonstrated that diabetes (DM) induces changes in the levels of several adypokines and this can worsen the prognosis of these subjects. However, the impact of DM in the context of a hypercaloric diet and its modulation by the chronic use of atorvastatin is not fully known. Aim: To evaluate, in a model of DM and hypercaloric diet, if chronic therapy with atorvastatin can modify serum levels of adiponectin. Materials and methods: GotoKakizaki (GK) diabetic rats (fed with a hypercaloric diet between 2 and 6 months) were divided in 2 groups (n = 10/group): AGKHD (not submitted to any drug), BGKHD A (fed with the same diet and treated with atorvastatin between 5 and 6 months of age). At 6 months of age, serum levels of adiponectin were determined using a non-com- petitive enzyme-linked imunossorbent assay (ELISA) technique. Results: Adiponectin levels were significantly lower in group B, when compared with GKHD animals (3.3 ± 0.2 versus 5.2 ± 0.3 μg/mL). Conclusion: In diabetic animals fed with a hypercaloric diet, chronic therapy with atorvastatin induces a significant decrease in adiponectin levels. Keywords: Diabetes mellitus; Nutrition; Inflammation doi:10.1016/j.yjmcc.2007.03.776 Effect of chronic metformin therapy in the mitochondrial function in an ex-vivo animal model of diabetes and hypercaloric diet submitted to global myocardial ischemiareperfusion Pedro Monteiro, Paulo Matafome, Marta Paiva, Raquel Carreira, Raquel Seiça, Lino Gonçalves, Luís A. Providencia. Basic Research Unit in Cardiology, Cardiology Department and Physio- logy Department, Coimbra Medical School, Coimbra, Portugal Aim: To evaluate, in a model of diabetes + hypercaloric diet + ischemiareperfusion (IR), if chronic therapy with MET improves cardiac mitochondrial function. Materials and methods: GotoKakizaki (GK) diabetic rats (fed with an hypercaloric diet between 2 and 6 months) were divided in 4 groups (n = 10/group): AGKHD control (no medication/no IR); BMET control (Metformin 10 mg/kg/day between month 5 and 6/no IR); CGKHD IR (as GKHD control and then IR); DMET IR (as MET control and then IR). At 6 months, hearts were removed and submitted to 165 min perfusion (control) or 10 min perfusion + 35 min ischemia +120 min reperfusion (IR). Mitochondrial parameters assessed were: oxidative stress (colorimetric thiobarbituric acid colori- metry testTBARS), mitochondrial swelling and calcium uptake (fluorimetry). Results: MET-treated rats had significantly lower oxidative stress levels during IR (0.94 ± 0.03 vs. 1.05 ± 0.02 nmol TBARS/mg protein; p < 0.05). MET-treated animals also showed a significant decrease in mitochondrial swelling in IR (57.7 ± 2.3 vs. 68.1± 1.8 arbitrary unitsAU; p < 0.05). MET therapy showed a trend towards an improvement in calcium uptake. Conclusion: In our model, MET improves cardiac mito- chondrial function, due to less oxidative stress and better ischemia tolerance. Keywords: Diabetes mellitus; Nutrition; Ischemiareperfusion doi:10.1016/j.yjmcc.2007.03.777 Impact of the chronic therapy with lipid lowering and antidiabetic drugs in the protein oxidative stress levels in an animal model of diabetes treated with an hypercaloric diet Pedro Monteiro, Paulo Matafome, Marta Paiva, Raquel Carreira, Raquel Seiça, Lino Gonçalves, Luís A. Providencia. Basic Research Unit in Cardiology, Cardiology Department and Physiology Department, Coimbra Medical School, Coimbra, Portugal Aim: To evaluate, in a model of DM fed with a hypercaloric diet, if the chronic use of lipid-lowering and antidiabetic drugs can alter the protein oxidative stress levels. Materials and methods: GotoKakizaki (GK) diabetic rats (fed with an hypercaloric diet between 2 and 6 months) were divided in 6 groups (n = 10/group): AGKHD (not submitted to any drug), BGKHD A (fed with the same diet and treated with atorvastatin between 5 and 6 months of age), CGKHD I (fed with the same diet and treated with insulin between 5 and 6 months of age), DGKHD M (fed with the same diet and treated with metformin between 5 and 6 months of age), EGKHD G (fed with the same diet and treated with gliclazide between 5 and 6 months of age) and FGKHD IA (fed with the same diet and treated with insulin + atorvastatin between 5 and 6 months of age). At 6 months, the level of carbonyl groups formation (an indicator of protein oxidative stress) was determined using a spectrophotometer. Results: The level of carbonyl groups formation showed a trend towards being lower in all the animal groups submitted to drug therapy, when compared to the GKHD. S60 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S55S71

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eccentric cardiac remodelling, but had no direct effect onglycaemic control. However the increased adiponectin levelspotentially indicate improved insulin signalling.

Keywords: Type II diabetes and obesity; Oxidative stress;Resistance training

doi:10.1016/j.yjmcc.2007.03.775

Effect of atorvastatin therapy in the adiponectin levels in ananimal model of diabetes and hypercaloric dietPedroMonteiro, PauloMatafome,Marta Paiva, Raquel Carreira,Raquel Seiça, Lino Gonçalves, Luís A. Providencia. BasicResearch Unit in Cardiology, Cardiology Department andPhysiology Department, Coimbra Medical School, Coimbra,Portugal

Introduction: Obese diabetics havemore and worse ischemicheart disease. It was already demonstrated that diabetes (DM)induces changes in the levels of several adypokines and this canworsen the prognosis of these subjects. However, the impact ofDM in the context of a hypercaloric diet and its modulation by thechronic use of atorvastatin is not fully known.

Aim: To evaluate, in a model of DM and hypercaloric diet, ifchronic therapy with atorvastatin can modify serum levels ofadiponectin.

Materials and methods: Goto–Kakizaki (GK) diabetic rats(fed with a hypercaloric diet between 2 and 6 months) weredivided in 2 groups (n=10/group): A—GKHD (not submitted toany drug), B—GKHDA (fed with the same diet and treated withatorvastatin between 5 and 6 months of age). At 6 months of age,serum levels of adiponectin were determined using a non-com-petitive enzyme-linked imunossorbent assay (ELISA) technique.

Results: Adiponectin levels were significantly lower ingroup B, when compared with GKHD animals (3.3±0.2 versus5.2±0.3 μg/mL).

Conclusion: In diabetic animals fed with a hypercaloric diet,chronic therapy with atorvastatin induces a significant decreasein adiponectin levels.

Keywords: Diabetes mellitus; Nutrition; Inflammation

doi:10.1016/j.yjmcc.2007.03.776

Effect of chronic metformin therapy in the mitochondrialfunction in an ex-vivo animal model of diabetes andhypercaloric diet submitted to global myocardialischemia–reperfusionPedro Monteiro, Paulo Matafome, Marta Paiva, Raquel Carreira,Raquel Seiça, Lino Gonçalves, Luís A. Providencia. BasicResearchUnit in Cardiology, CardiologyDepartment and Physio-logy Department, Coimbra Medical School, Coimbra, Portugal

Aim: To evaluate, in a model of diabetes+hypercaloricdiet+ ischemia–reperfusion (IR), if chronic therapy with MET

improves cardiac mitochondrial function. Materials andmethods: Goto–Kakizaki (GK) diabetic rats (fed with anhypercaloric diet between 2 and 6 months) were divided in 4groups (n=10/group): A—GKHD control (no medication/noIR); B—MET control (Metformin 10 mg/kg/day betweenmonth 5 and 6/no IR); C—GKHD IR (as GKHD control andthen IR); D—MET IR (as MET control and then IR). At6 months, hearts were removed and submitted to 165 minperfusion (control) or 10 min perfusion +35 min ischemia+120 min reperfusion (IR). Mitochondrial parameters assessedwere: oxidative stress (colorimetric thiobarbituric acid colori-metry test—TBARS), mitochondrial swelling and calciumuptake (fluorimetry).

Results: MET-treated rats had significantly lower oxidativestress levels during IR (0.94±0.03 vs. 1.05±0.02 nmolTBARS/mg protein; p<0.05).MET-treated animals also showeda significant decrease in mitochondrial swelling in IR (57.7±2.3vs. 68.1±1.8 arbitrary units—AU; p<0.05). MET therapyshowed a trend towards an improvement in calcium uptake.

Conclusion: In our model, MET improves cardiac mito-chondrial function, due to less oxidative stress and betterischemia tolerance.

Keywords: Diabetes mellitus; Nutrition; Ischemia–reperfusion

doi:10.1016/j.yjmcc.2007.03.777

Impact of the chronic therapy with lipid lowering andantidiabetic drugs in the protein oxidative stress levels in ananimal model of diabetes treated with an hypercaloric dietPedroMonteiro, PauloMatafome,Marta Paiva, Raquel Carreira,Raquel Seiça, Lino Gonçalves, Luís A. Providencia. BasicResearch Unit in Cardiology, Cardiology Department andPhysiology Department, Coimbra Medical School, Coimbra,Portugal

Aim: To evaluate, in a model of DM fed with a hypercaloricdiet, if the chronic use of lipid-lowering and antidiabetic drugscan alter the protein oxidative stress levels.

Materials and methods: Goto–Kakizaki (GK) diabetic rats(fed with an hypercaloric diet between 2 and 6 months) weredivided in 6 groups (n=10/group): A—GKHD (not submittedto any drug), B—GKHD A (fed with the same diet and treatedwith atorvastatin between 5 and 6 months of age), C—GKHD I(fed with the same diet and treated with insulin between 5 and6 months of age), D—GKHD M (fed with the same diet andtreated with metformin between 5 and 6 months of age), E—GKHD G (fed with the same diet and treated with gliclazidebetween 5 and 6 months of age) and F—GKHD IA (fed with thesame diet and treated with insulin+atorvastatin between 5 and6 months of age). At 6 months, the level of carbonyl groupsformation (an indicator of protein oxidative stress) wasdetermined using a spectrophotometer.

Results: The level of carbonyl groups formation showed atrend towards being lower in all the animal groups submitted todrug therapy, when compared to the GKHD.

S60 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S55–S71