A study comparing the effects of rosiglitazone and/or insulin treatments on streptozotocin induced diabetic (type I diabetes) rat aorta and cavernous tissues.

Our aim was to investigate the role of oxidative stress and inflammation on the functional and biochemical changes caused by hyperglycemia in the aorta and corpus cavernosum tissues of streptozotozin diabetic rats and to determine if rosiglitazone and/or insulin treatment has any preventive effect on organ dysfunction. Wistar Albino rats were divided into 2 groups. I) Control group: a) Vehicle, 0.1 M citrate buffer, the solvent of streptozotocin injected intraperitoneally (i.p) and b) Rosiglitazone group: (4 mg/kg/day, i.p.) for 8 weeks. II) Diabetic group: streptozotocin (60 mg/kg) was administered i.p. to induce diabetes. 48 h after streptozotocin injection, animals were divided into 4 subgroups (n=6 for each group); a) no treatment group (D), b) treated with rosiglitazone (4 mg/kg/day) (DR), c) treated with insulin (6 U/kg/day) (DI) and d) treated with insulin and rosiglitazone (DRI) for 8 weeks. At the end of the experimental period, animals were decapitated and tissue samples were collected for in vitro experiments and biochemical studies. Endothelium dependent relaxation induced by acetylcholine in the aorta and corpus cavernosum tissues were attenuated in the diabetic group, whereas phenylephrine induced contractile responses were reduced. These responses were restored after rosiglitazone and/or insulin treatment, the combination being the most efficient treatment. Malondialdehyde and TNF-α levels were increased in diabetic rats while glutathione levels were decreased. All treatments prevented these changes in biochemical parameters, rosiglitazone and insulin combination again being the most efficient treatment. Our results suggested that supplementing diabetic patients receiving insulin treatment with adjunct therapy of rosiglitazone may have some benefit for controlling diabetic complications.

Elçioğlu HK ，Kabasakal L ，Özkan N ，Çelikel Ç ，Ayanoğlu-Dülger G ... -  《-》

Melatonin treatment protects against diabetes-induced functional and biochemical changes in rat aorta and corpus cavernosum.

Paskaloglu K ，Sener G ，Ayanğolu-Dülger G 《EUROPEAN JOURNAL OF PHARMACOLOGY》

Changes in caveolin-1 expression and vasoreactivity in the aorta and corpus cavernosum of fructose and streptozotocin-induced diabetic rats.

Hyperglycemia is a common defining feature in the development of endothelial dysfunction which plays a key role in the pathogenesis of both type 1 and type 2 diabetes. Caveolin-1 is the main structural component of caveolae which might be involved in the pathophysiology of macrovascular complications of diabetes. In this study we aimed to observe the effect of caveolin-1 on functional responses of aorta and corpus cavernosum in the streptozotocin and fructose-induced diabetes groups. Type 1 diabetes was induced by intraperitoneal administration of streptozotocin (60 mg/kg),. Type 2 diabetes by adding fructose in the rat's drinking water (10% (w/v)) for 8 weeks. For insulin treatment; rats were treated with insulin (6 U/kg) for 8 weeks. In Type I and Type II diabetic groups the contractile responses of corpus cavernosum strips to phenylephrine (EC(50):1.82 x 10(-5)M;1.47 x 10(-5)M, respectively)and relaxation responses to acetylcholine (EC(50):7.5 x 10(-5)M;4.48 x 10(-5)M, respectively)were significantly impaired. Contractile responses of aorticstrips to phenylephrine in diabetic groups were markedly decreased (EC(50):3.7.10(-7)M;2.61.10(-7)M respectively) and dose-dependent relaxation responses to acetylcholine were also attenuated (EC(50):3.23.10(-6)M; 2.0.10(-6)M respectively). Treatment with insulin improved the functional responses in the aorta and corpus cavernosum. Protein expression of caveolin-1 was increased in the aorta and corpus cavernosum of the diabetic groups, but this increase seen in the streptozotocin group was more significant than the fructose group. Our findings indicate that an attenuation of the functional responses in both diabetes groups were probably associated with an enhanced expression of caveolin-1, and therefore a decrease in the eNOS activity with a concomitant decrease in NO synthesis.

Elçioğlu KH ，Kabasakal L ，Cetinel S ，Conturk G ，Sezen SF ，Ayanoğlu-Dülger G ... -  《-》

Alpha-lipoic acid treatment ameliorates metabolic parameters, blood pressure, vascular reactivity and morphology of vessels already damaged by streptozotocin-diabetes.

The present study investigated the effects of alpha-lipoic acid treatment (50 mg/kg/day) on the metabolism and vascular condition already damaged by streptozotocin (STZ)-diabetes in rats. Carbohydrate and lipid metabolism, oxidative stress and antioxidant status were assessed in non-diabetic controls, 12-week untreated diabetic and 12-week treated diabetic (untreated for 6 weeks and then treated with alpha-lipoic acid for the last 6 weeks) rats. Blood pressures of rats were measured by tail-cuff method. Vascular reactivity was evaluated in isolated aortic rings. Morphology of aorta was examined by electron microscopy technique. Alpha-lipoic acid treatment effectively reversed body weight, blood glucose, plasma insulin, cholesterol, triglycerides and lipid peroxidation levels of diabetic animals. STZ-diabetes resulted in increased blood pressure, which was partially improved by alpha-lipoic acid treatment. Although the superoxide dismutase (SOD) activity in aortic homogenates was not changed by diabetes or antioxidant treatment, catalase or glutathione peroxidase (GPx) activity significantly increased in untreated diabetic rats. Alpha-lipoic acid treatment improved catalase activity in diabetic aorta. The contractile effect of phenylephrine markedly increased in diabetic rings, which was completely reversed by alpha-lipoic acid treatment. The maximum vasorelaxant response of pre-contracted aortic rings exposed to cumulatively increased concentrations of acetylcholine was unaffected by diabetes or antioxidant treatment. Sodium nitroprusside-induced endothelium-independent relaxations were similar in all experimental groups. Various alterations caused by STZ-diabetes in aorta structure were partially ameliorated by alpha-lipoic acid treatment. The potency of alpha-lipoic acid on the reversal of hypertension by affecting vascular reactivity and morphology as well as general metabolism of diabetic rats confirms the importance of hyperglycemia-induced oxidative stress in the development of diabetes-induced vascular complications and suggests a potential therapeutic approach.

Koçak G ，Aktan F ，Canbolat O ，Ozoğul C ，Elbeğ S ，Yildizoglu-Ari N ，Karasu C ，ADIC Study Group--Antioxidants in Diabetes-Induced Complications ... -  《diabetes nutrition & metabolism》

Simvastatin treatment restores vasoconstriction and the inhibitory effect of LPC on endothelial relaxation via affecting oxidizing metabolism in diabetic rats.

Oxidative stress and dyslipidaemia play an important role in the development of diabetes-induced vascular complications. The aim of this study was to examine the reversal effects of simvastatin on some metabolic and oxidative parameters, and vascular functions in diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Eight weeks after STZ induction, some of the diabetic and control rats were treated with simvastatin (10 mg/kg rat/d) for 4 weeks. Plasma glucose, triglyceride and total cholesterol concentrations were significantly increased in 12-week diabetic rats. Simvastatin treatment stopped the loss of body weight, completely normalized the increase of plasma lipids and partially reduced the hyperglycaemia in diabetic rats. Increased malondialdehyde levels, catalase and glutathione peroxidase activities were normalised by simvastatin treatment in diabetic aorta. Phenylephrine (PE)-induced contractility in aorta rings was unaffected by diabetes, but was markedly decreased after simvastatin treatment in both control and diabetic rats. Reduction of endothelium-dependent vasorelaxation in diabetes was significantly ameliorated by simvastatin treatment. Incubation of aorta rings with lysophosphatidylcholine, a component of the oxidized LDL, did not significantly affect PE-induced contractions, but reduced endothelium-dependent relaxations more in untreated-diabetic rats than in other experimental groups. The endothelium-independent vasorelaxations were similar in all ring preparations. These results indicate that simvastatin treatment may ameliorate diabetes-induced abnormal vasoconstriction and endothelial dysfunction via affecting general and oxidizing metabolism, nitric oxide disability and intracellular calcium mobilisation.

Ceylan A ，Karasu C ，Aktan F ，Ozansoy G ... -  《diabetes nutrition & metabolism》