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

Conclusion: In diabetic animals fed with a hypercaloric diet,the chronic use of lipid-lowering and antidiabetic drugs leads toa mild decrease in the protein oxidative stress.

Keywords: Diabetes mellitus; Nutrition; Oxidative metabolites

doi:10.1016/j.yjmcc.2007.03.778

Mitochondrial signaling in diabetic rat heart: Acute phaseof the diseaseAttila Ziegelhoeffer1, Olga Pechanova2, Miroslav Ferko1,Terezia Holotnakova3, Jana Mujkosova1, Iveta Waczulikova4,Silvia Pastorekova3. 1Inst. Heart Res. 2Inst. Norm. and Pathol.Physiol., Slovakia. 3Inst. Virol., S.A.S., Slovakia. 4FMPI,Comenius University; Bratislava, Slovakia

Background: Streptozotocin (STZ) diabetes (DIA) inducespathological but also compensatory changes in heart (H) mito-hondria (MIT).

Aims: i.) Elucidation of mechanisms and outcome of STZ-DIA-induced functional alterations in H-MIT, ii.) Investigationof signals by which DIA-H-MITcrosstalk with other subcellularorganells.

Experimental: DIA induced in male Wistar rats (220±20 gb.wt.) by 65 mg kg− 1 STZ i.p., w as terminated on 8th day afterSTZ application. MIT were isolated by differential centri-fugation+protease. Estimations: MIT function, MIT-NO-synthase, conjugated dienes and membrane fluidity. MIT-signaling towards hypoxic genes (carbonic anhydrase, CA IXexpression by RT PCR) was studied with diazoxide (DZO),tempol (TL), bongkrekic acid (BA) and N-acetylcystein (NAC)as modulators.

Results and discussion:Metabolic control of DIA-increase inglucose, glycohemoglobin, triacylglycerols, cholesterol and de-crease in insulin: +235.8, +89.5, +270.4, +53.6 and −53.9%respectively. MIT O2 consumption, phosphorylation rate and NOsynthase activity were also decreased (p<0.05). DZO and TLstimulated CA IX expression, the former via inducing accumula-tion of succinate followed by its release fromMIT, the latter maybe by acting as prooxidant. NAC as antioxidant and BA as in-hibitor of ROS release from MIT prevented CA IX expression.

Conclusions: In acute DIA, H-MIT are signaling by re-leasing radicals and succinate also towards expression ofhypoxic genes. Increased NO-signaling was not confirmed.Grants: APVV 51-027404, 51-017902; VEGA 2/7126/27.

Keywords: Mitochondrial signaling; Diabetic heart; Carbonicanhydrase expression

doi:10.1016/j.yjmcc.2007.03.779

Potassium fluxes and energy metabolism in beating diabeticrat heartsO. Jilkina1,2, B. Kuzio1, V.V. Kupriyanov1,2. 1IBD NRC,Canada. 2University of Manitoba, Winnipeg, Canada

Consequences of 7-week streptozotocin-induced diabetesmellitus (DM) were evaluated in Langendorff-perfused rathearts using non-invasive methods: 1) 87Rubidium NMR (Rb+

is a K+ tracer) to follow kinetics of Rb+/K+ uptake and effluxin the hearts, 2) 31P NMR to monitor high-energy phosphatesand intracellular pH, and 3) optical spectroscopy to detect a603 nm peak in myocardial absorbance spectra (A603–620, anindex of cyt c oxidase redox state). In DM hearts, basal Rb+

uptake was inhibited by ∼15% (Table 1) due to a decrease inthe activity of Na+/K+ ATPase and/or changes in the Na+

uptake pathways. Rb+ efflux, activated by a KATP channelopener, P-1075, was lower in diabetic hearts by ∼20% (Table1), due to a decrease either in numbers or sensitivity of KATP

channels. DM hearts (n=7) were more resistant to a mito-chondrial uncoupler 2,4-dintrophenol (DNP, 50 μM, 20 min):ATP decreased to 67±10% and PCr to 49±6% in diabetic vs.33±15% and 34±13% in control hearts (n=4), respectively;pHi decreased by ∼0.2 in control and by ∼0.1 pH units in DMhearts. Cyt c oxidase was less reduced in DNP-treated diabetichearts: A603–620 =0.077±0.011 (n=8), A603–620 =0.101±0.022(n=6) in control.

Table 1Effects of DM on Rb +/K+ transport. Rate constants of Rb+ uptake and efflux arepresented (×10−3, min−1)

Group (n) Control Diabetic

kuptake, baseline 57±5 (16) 49±11 (19), p<0.02kefflux, baseline 44±4 (3) 41±2 (4)kefflux, P-1075 (5 μM) 74±17 (6) 60±9 (7)

Conclusions: Regulation of K+ transport by Na+/K+ ATPaseand KATP channels is altered and sensitivity to mitochondrialuncoupling is reduced in diabetic rat hearts.

Keywords: Diabetes mellitus; Metabolism; Potassium

doi:10.1016/j.yjmcc.2007.03.780

De novo experimental animal model of metabolicsyndrome*ShuGuang Lin1, XiaoZhong Huang1, XiYong Yu1, HongWenFei1, YongHeng Fu1, XiaoYing Liu1, WeiKang Wu2. 1Guang-dong Provincial People's Hospital, China. 2Sun Yet-SumUniversity, Guangzhou 510080, China

To establish a mimic animal model of metabolic syndromefor exploring the mechanisms and therapeutic effects ofmedicine. Adult spontaneously hypertensive rats (SHR) andWistar rats were randomly divided into four groups: group A(SHR control) and C (Wistar control) were fed with standardchow diet, group B (SHR) and D (Wistar) were fed with high fatdiet. The specimens harvested at 0 day and 4 weeks after beenfed with different diet were measured and studied. Results:The blood pressure, fasting Blood glucose in group A and Bwere significantly increased than those in group C and D. CRPin group A, B was also higher than that in group C and D.

S61ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S55–S71