Therapeutic effect of green tea extract on oxidative stress in aorta and heart of streptozotocin diabetic rats

Hyperglycemia induced oxidative stress has been proposed as a cause of many complications of diabetes including cardiac dysfunction. The present study depicts the therapeutic effect of green tea extract on oxidative stress in aorta as well as heart of streptozotocin diabetic rats. Six weeks after diabetes induction, green tea was administered orally for 4 weeks [300 mg (kg body weight)(-1) day (-1)]. In aorta and heart of diabetic rats there was a significant increase in the activity of superoxide dismutase, catalase and glutathione peroxidase with an increase in lipid peroxides. Diabetic rats showed a significant decrease in the levels of serum and cardiac glutathione. Green tea administration to diabetic rats reduced lipid peroxides and activity of antioxidant enzymes whereas increased glutathione content. The results demonstrate that the induction of antioxidant enzymes in diabetic rats is not efficient and sufficient to reduce the oxidative stress. But green tea by providing a competent antioxidative mechanism ameliorates the oxidative stress in the aorta and heart of diabetic rats. The study suggests that green tea may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus.     

Effect of cobalt on the oxidative status in heart and aorta of streptozotocin-induced diabetic rats

Effects of cobalt on the antioxidant status of control and streptozotocin diabetic rat heart and aorta were examined at the second, fourth and sixth week of treatment. Rats were divided into four groups: control, diabetic, control treated with cobalt chloride and diabetic treated with cobalt chloride. Diabetes was induced by tail vein injection of streptozotocin (STZ). Cobalt treatment groups were given 0.5 mM of CoCl(2) in drinking water. The rats in both groups were further subdivided into three groups of six rats each. Rats in these subgroups were studied at 2-week intervals up to 6 weeks. At the end of the experiment, all animals were sacrificed by decapitation, heart and aorta samples were removed for determination of thiobarbituric acid reactive substance (TBARS) level and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. It was found that lipid peroxidation levels and antioxidant enzyme activities were increased in the streptozotocin-induced diabetic rats at all times studied. Cobalt treatment of diabetic rats (0.5 mM in drinking water) resulted in attenuation of the increased levels of TBARS and antioxidant enzyme activities in heart and aorta. Thus, the effect of oral administration of cobalt at this dose during the early stage of experimental diabetes can be considered as a consequence of altered endogenous defence mechanisms in heart and aorta.     

Effects of diabetes on glucose oxidation in rat aorta after hypophysectomy and adrenalectomy

The influence of diabetes, hypophysectomy and adrenalectomy on glucose oxidation in rat aorta was studied. Diabetes was induced in normal, adrenalectomized and hypophysectomized-cortisone substituted rats by streptozotocin (65 mg/kg body weight). The oxidation of glucose to CO2 was determined during incubation of rat aorta in vitro for 2-3 hours. The aortic glucose oxidation was reduced after hypophysectomy but was unaffected by adrenalectomy. After streptozotocin treatment the rise in blood glucose concentration was similar in normal, adrenalectomized and hypophysectomized-cortisone substituted rats. In shamoperated diabetic rats the aortic glucose oxidation was reduced after a diabetes duration of 4 days. In adrenalectomized diabetic rats the aortic glucose oxidation was not significantly affected after 4 days but was reduced after a diabetes duration of 14 days. When adrenalectomized diabetic rats were treated with hydrocortisone the aortic glucose oxidation was reduced after diabetes for 4 days. After incubation of normal rat aorta in vitro for 6 hours with cortisol (1 microgram/ml) in the incubation medium a decrease in the aortic glucose oxidation was found. Incubation of aorta with only growth hormone had no effect. These results suggest that cortisol is of importance for the lowered glucose oxidation in diabetic rat aorta.     

The effects of n-stearoylethanolamine on the NO-synthase pathway of NO generation in the aorta and heart of streptozotocin-induced diabetic rats

The aim of the presented experiments was to study the influence of suturated NAE--N-stearoylethanolamine (NSE) on the NO synthesis by NO-synthases in aorta and heart tissues of rats with developmental (12-week) streptozotocin-induced (50 mg/kg of body weight) diabetes. Also we evaluated the state of endothelium-dependent relax reactions of aorta smooth muscles. It was shown that the development of diabetes is accompanied with disbalance of NO-synthesis wich consist in inducible NOS (iNOS) activation and inhibition of constitutive NOS (cNOS) and arginase activities. The aorta smooth muscle endothelium-dependent relax reactions were decreased in diabetic rats. The NSE administration to rats with development streptozotocin-induced diabetes resulted in inhibition of iNOS activity and elevation of cNOS and arginase activities in these tissues. Normalization of NO-synthesis under NSE action was accompanied with restoration of aorta smooth muscle endothelium-dependent relax reactions in diabetic rats.     

Pentose phosphate pathway,glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E

The aim of the present study was to investigate the effects of treatment with antioxidant stobadine (ST) on the activities of enzymes related with pentose phosphate pathway and glutathione-dependent metabolism and the other markers of oxidative stress in brain and peripheral organs of diabetic rats, and to compare the effects of ST treatment alone with the effects of treatments with another antioxidant vitamin E and ST plus vitamin E. Rats were made diabetic by the injection of streptozotocin (STZ; 55 mg/kg IP), and, 2 days later, some control and diabetic rats were left untreated or treated with ST (24.7 mg/kg/day, orally), vitamin E (400–500 U/kg/day, orally), or both substances together. In the brain, although 6-phosphogluconate dehydrogenase activity (6-PGD) did not change, glucose-6-phosphate dehydrogenase activity (G-6PD) was markedly increased in diabetic rats compared with controls; only combined treatment with ST and vitamin E produced a partial prevention on this alteration. The aorta G-6PD and 6-PGD of diabetic rats were 52% and 36% of control values, respectively. Neither single treatments with each antioxidant nor their combination altered the G-6PD and 6-PGD in aorta of diabetic rats. Glutathione peroxidase (GSHPx) activity was increased by STZ-diabetes in brain, heart, and kidney. In diabetic brain, vitamin E alone or combination with ST kept GSHPx at normal levels. Diabetes-induced stimulation in GSHPx did not decrease in response to the treatment with vitamin E in heart and kidney, but was greatly prevented by ST alone. The activity of glutathione reductase (GR) was decreased in brain and heart of diabetic rats. The treatment with each antioxidant or with a combination of both agents completely prevented this deficiency and resulted in further activation of GR in diabetic tissues. Glutathione S-transferase (GST) activity did not significantly change in diabetic brain and aorta. GST was stimulated by all treatment protocols in the brain of diabetic rats and was depressed in aorta of control rats. Catalase (CAT) was activated in diabetic heart but depressed in diabetic kidney. Diabetes-induced abnormalities in CAT activity did not respond to vitamin E alone in heart, was moderately ameliorated by the treatment with this vitamin in kidney, and was completely prevented by ST alone in both tissues. Superoxide dismutase (SOD) activity of brain and heart was unchanged by the diabetes but inhibited in diabetic kidney after the treatment ST alone or ST plus vitamin E. The lipid peroxidation (MDA) was increased in diabetic brain and heart. ST or vitamin E alone partly prevented diabetes-induced increase in MDA in brain and heart; however, antioxidant combination achieved a completely amelioration in MDA of these tissues of diabetic rats. Kidney MDA levels were similar in control and untreated diabetic animals. ST and vitamin E treatments, when applied separately or together, significantly reduced kidney MDA in both control and diabetic rats; and the combined effect of antioxidants was greater than that of each alone. These results are consistent with the degenerative role of hyperglycemia on cellular reducing equivalent homeostasis and antioxidant defense, and provide further evidence that pharmacological intervention of different antioxidants may have significant implications in the prevention of the prooxidant feature of diabetes and protects redox status of the cells.     

Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats

Lipid disorders and increased oxidative stress may exacerbate some complications of diabetes mellitus. Previous studies have implicated the beneficial effects of some antioxidants, omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the protection of cells from the destructive effect of increased lipids and lipid peroxidation products. This study, therefore, was designed to investigate the effects of cod liver oil (CLO, Lysi Ltd. Island), which comprises mainly vitamin A, PUFAs, EPA and DHA. Effects were monitored on plasma lipids, lipid peroxidation products (MDA) and the activities of antioxidant enzymes, glutathione peroxidase (GSHPx) and catalase in heart, liver, kidney and lung of non-diabetic control and streptozotocin (STZ)-induced-diabetic rats. Two days after STZ-injection (55 mg kg(-1) i.p.), non-diabetic control and diabetic rats were divided randomly into two groups as untreated or treated with CLO (0.5 ml kg(-1) rat per day) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic animals; CLO treatment almost completely prevented these abnormalities in triacylglycerol and cholesterol, but hyperglycaemia was partially controlled. CLO also provided better weight gain in diabetic animals. In untreated diabetic rats, MDA markedly increased in aorta, heart and liver but was not significantly changed in kidney and lung. This was accompanied by a significant increase in both GSHPx and catalase enzyme activities in aorta, heart, and liver of diabetic rats. In kidney and lung, diabetes resulted in reduced catalase while GSHPx was significantly activated. In aorta, heart, and liver, diabetes-induced changes in MDA were entirely prevented by CLO treatment. In the tissues of CLO-treated diabetic animals, GSHPx activity paralleled those of control animals. CLO treatment also caused significant improvements in catalase activities in every tissue of diabetic rats, but failed to affect MDA and antioxidant activity in control animals. The current study suggests that the treatment of diabetic rats with CLO provides better control of glucose and lipid metabolism, allows recovery of normal growth rate, prevents oxidative/peroxidative stress and ameliorates endogenous antioxidant enzyme activities in various tissues. Because CLO contains a plethora of beneficial compounds together, its use for the management of diabetes-induced complications may provide important advantages.     

Alkaline, Endo III and FPG modified comet assay as biomarkers for the detection of oxidative DNA damage in rats with experimentally induced diabetes

Increased production of reactive oxygen species under diabetic condition underlines the higher oxidatively damaged DNA in different tissues. However, it is practically difficult to assess the oxidatively damaged DNA in different internal organs. Therefore, the present study was aimed to evaluate the extent of oxidative stress-induced DNA damage in different organs with the progression of diabetes. Diabetic and control Sprague Dawley rats were sacrificed in time-dependent manner and the lung, liver, heart, aorta, kidney, pancreas and peripheral blood lymphocytes (PBL) were analyzed for both alkaline and modified comet assay with endonuclease-III (Endo III) and formamidopyrimidine-DNA glycosylase (FPG) (hereafter called modified comet assay) for the detection of oxidative DNA damage. The statistically significant increase in olive tail moment (OTM) was found in all the tested tissues. The extent of DNA damage was increased with the progression of diabetes as revealed by the parameter of OTM in alkaline and modified comet assay. Further, the positive correlations were observed between OTM of the lung, liver, heart, aorta, kidney and pancreas with PBL of diabetic rat in the alkaline and modified comet assay. Moreover, significant increase in the 8-oxodG positive nuclei in the lung, liver, heart, aorta, kidney and pancreas was observed in 4th and 8th week diabetic rat as compared to control. Results of the present study clearly indicated the suitability of alkaline and modified comet assay for the detection of multi-organ oxidative DNA damage in streptozotocin (STZ)-induced diabetic rat and showed that damaged DNA of PBL can be used as a suitable biomarker to assess the internal organs response to DNA damage in diabetes.     

Effect of telmisartan on the expression of adiponectin receptors and nicotinamide adenine dinucleotide phosphate oxidase in the heart and aorta in type 2 diabetic rats

ABSTRACT: BACKGROUND: Diabetic cardiovascular disease is associated with decreased adiponectin and increased oxidative stress. This study investigated the effect of telmisartan on the expression of adiponectin receptor 2 (adipoR2) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits in the heart and the expression of adiponectin receptor 1 (adipoR1) in aorta in type 2 diabetic rats. METHODS: Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). Heart function, adipoR2, p22phox, NOX4, glucose transporter 4(GLUT4), monocyte chemoattractant protein-1(MCP-1) and connective tissue growth factor CTGFin the heart, and adipoR1, MCP-1 and nuclear factor kappa B (NF-kappaB) in aorta were analyzed in controls and diabetic rats treated with or without telmisartan (5mg/kg/d) by gavage for 12 weeks. RESULTS: Heart function, plasma and myocardial adiponectin levels, the expression of myocardial adipoR2 and GLUT4 were significantly decreased in diabetic rats (P<0.05). The expression of myocardial p22phox, NOX4, MCP-1, and CTGF was significantly increased in diabetic rats (P<0.05). The expression of adipoR1 was decreased and the expression of MCP-1 and NF-kappaB was increased in the abdominal aorta in diabetic rats (P<0.05). Telmisartan treatment significantly attenuated these changes in diabetic rats (P<0.05). CONCLUSIONS: Our results suggest that telmisartan upregulates the expression of myocardial adiponectin, its receptor 2 and GLUT4. Simultaneously, it downregulates the expression of myocardial p22phox, NOX4, MCP-1, and CTGF, contributing so to the improvement of heart function in diabetic rats. Telmisartan also induces a protective role on the vascular system by upregulating the expression of adipoR1 and downregulating the expression of MCP-1 and NF-kappaB in the abdominal aorta in diabetic rats. KEYWORDS: Telmisartan; Adiponectin receptor; NADPH oxidase; Type 2 diabetic; Cardiac; Aorta.     

Tissue-specific expression of PPAR mRNAs in diabetic rats and divergent effects of cilostazol

Cilostazol and ligands of peroxisome proliferator-activated receptors (PPARs) have been effectively used to alleviate diabetic complications, but the common and tissue-specific expression patterns of PPARs in different tissues in diabetic patients and those treated with cilostazol have not been reported. Here, we aimed to assess the effects of diabetes and cilostazol on mRNA expression of PPARalpha and PPARgamma in the aorta, renal cortex, and retina of diabetic rats treated with cilostazol for 8 weeks. PPARalpha mRNA expression showed uniform downregulation in all these tissues in diabetic rats, and this effect was reversed by cilostazol treatment. Surprisingly, PPARgamma mRNA expression was reduced in the renal cortex and retina, yet increased in the aorta of diabetic rats, although cilostazol still reversed these changes. Interestingly, cilostazol, a well-known phosphodiesterase 3 inhibitor and cAMP elevator, augmented cAMP content only in the aorta, but showed no significant effects in the renal cortex of diabetic rats. In conclusion, mRNA expression of PPARs is tissue-specific in diabetes and may be differently affected by cilostazol, possibly because of its tissue-specific effects on cAMP content.     

Iron Increases Diabetes-Induced Kidney Injury and Oxidative Stress in Rats

Diabetic nephropathy is both a common and a severe complication of diabetes mellitus. Iron is an essential trace element. However, excess iron is toxic, playing a role in the pathogenesis of diabetic nephropathy. The present study aimed to determine the extent of the interaction between iron and type 2 diabetes in the kidney. Male rats were randomly assigned into four groups: control, iron (300-mg/kg iron dextran), diabetes (a single dose of intraperitoneal streptozotocin), and iron + diabetes group. Iron supplementation resulted in a higher liver iron content, and diabetic rats showed higher serum glucose compared with control rats, which confirmed the model as iron overload and diabetic. It was found that iron + diabetes group showed a greater degree of kidney pathological changes, a remarkable reduction in body weight, and a significant increase in relative kidney weight and iron accumulation in rat kidneys compared with iron or diabetes group. Moreover, malondialdehyde values in the kidney were higher in iron + diabetes group than in iron or diabetes group, sulfhydryl concentration and glutathione peroxidase activity were decreased by the diabetes and iron + diabetes groups, and protein oxidation and nitration levels were higher in the kidney of iron + diabetes group as compared to iron or diabetes group. However, iron supplementation did not elevate the glucose level of a diabetic further. These results suggested that iron increased the diabetic renal injury probably through increased oxidative/nitrative stress and reduced antioxidant capacity instead of promoting a rise in blood sugar levels; iron might be a potential cofactor of diabetic nephropathy, and strict control of iron would be important under diabetic state.     

Dysfunction of soluble guanylyl cyclase in aorta and kidney of Goto-Kakizaki rats: influence of age and diabetic state.

Type 2 diabetes mellitus is frequently associated with arterial hypertension. The mechanisms involved in this association are not known in detail, but endothelial dysfunction and a blunted vascular response to endogenous vasodilators are thought to play a role. In the present study we investigated the in vitro activity of vascular and renal soluble guanylyl cyclase in type 2 diabetic Goto-Kakizaki rats aged 5, 15, and 30 weeks, in comparison with age-matched Wistar controls. Blood pressure was monitored by radiotelemetry, and serum glucose and insulin concentrations were measured by standard assays. Goto-Kakizaki rats of all age groups had serum glucose concentrations significantly higher than those of corresponding Wistar controls. Serum insulin was unchanged until 15 weeks of age and was elevated in the 30-week-old diabetic rats. Blood pressure in Goto-Kakizaki rats was significantly higher than that in Wistar controls, and heart rate was significantly lower. Mesenteric arteries of diabetic rats showed a blunted relaxation in response to acetylcholine and sodium nitroprusside. In aortic tissue from Wistar rats an age-dependent increase was found in nitric oxide-stimulated cGMP formation, which was absent in the diabetic animals. Moreover, the maximum activity of soluble guanylyl cyclase was significantly lower in Goto-Kakizaki rats in all age groups studied. In renal tissue no differences were found between diabetic and control rats, except at 30 weeks of age when Goto-Kakizaki rats showed a significant reduction in basal and stimulated guanylyl cyclase activity. In conclusion, the present study shows a persistent reduction in vascular nitric oxide-sensitive guanylyl cyclase in Goto-Kakizaki rats, which occurred shortly after weaning and may contribute to the elevation in blood pressure in this strain of genetically diabetic rats.     

Cardiovascular system of offsprings of hypertensive rats with defective nitric oxide production

The question was addressed of how nitric oxide synthase (NO synthase) inhibition-induced hypertension in rat parents would affect the cardiovascular system in their offsprings. Two experimental groups were set up: Group I -- offsprings of parents who had both been administered NO synthase inhibitor L-nitro-arginine methyl ester (L-NAME 40 mg/kg/day) for 5 weeks, the treatment of dams continued till week 12. Group II -- offsprings fed by dams administered L-NAME after delivery only for a period of 4 weeks. Control age-matched offsprings formed the third group. Blood pressure and heart rate in parents and in 3-week-old offsprings were determined noninvasively. In the offsprings, body and heart weight were measured and the heart/body weight ratio (HW/BW) was calculated. The NO synthase activity, and also ornithine decarboxylase activity as a marker of polyamine production, were determined in the heart. The acetylcholine-induced relaxation of aortic rings was also followed. A marked blood pressure increase with a tendency to a decreased heart rate was found in the offsprings of Group I. A significant decrease in heart weight and body weight with a decreased HW/BW ratio indicated cardiac hypotrophy that contrasted with the decrease in NO synthase activity and increase in ornithine decarboxylase activity in the heart. Noteworthy was also the finding of completely preserved relaxation of the aorta to acetylcholine. Offsprings of Group II were similarly characterized by significantly higher blood pressure, a tendency to decreased heart rate, a decrease in heart weight, but not of the HW/BW ratio. The contrasting findings of heart weight decrease on the one hand and NO synthase activity decrease and ornithine decarboxylase increase on the other, were also found in this group. Full relaxation of the aorta to acetylcholine was preserved. It can be concluded that remarkable alterations in the cardiovascular system were found in offsprings of hypertensive NO compromised parents.     

Ghrelin and insulin gene expression changes in streptozotocin-induced diabetic rats after rosiglitazone pretreatment

The aim of the study was to evaluate the effect of rosiglitazone treatment on islet ghrelin and insulin gene expressions in streptozotocin (STZ)-induced diabetic rats. Animals were divided into four groups. 1. Intact controls. 2. Rosiglitazone-treated controls. 3. STZ-induced diabetes. 4. Rosiglitazone-treated diabetes. Rosiglitazone was given for 7 days at a dose of 20 mg/kg body weight. Ghrelin and insulin gene expressions were investigated by immunohistochemistry and in situ hybridization. There was no statistically significant difference in body weight between STZ-induced diabetic rats and rosiglitazone-treated diabetic rats during the experimental period. Furthermore, there were no significant differences in blood glucose levels and insulin immunoreactive cell numbers between STZ-induced diabetic rats and rosiglitazone-treated diabetic rats. There was a tendency towards a reduction of ghrelin gene expression in diabetic animals compared with intact controls. We found, in addition, that ghrelin immunoreactive and ghrelin mRNA expressing cells were frequent in the epithelial lining of the ducts suggesting ductal epithelium might be the source of the regenerating islet ghrelin cells, as is known for other islet cells. The results show that short-term rosiglitazone pretreatment had no significant effect on ghrelin and insulin gene expressions.     

Enhanced permeability transition explains the reduced calcium uptake in cardiac mitochondria from streptozotocin-induced diabetic rats

Cardiac dysfunction is associated with diabetes. It was previously shown that heart mitochondria from diabetic rats have a reduced calcium accumulation capacity. The objective of this work was to determine whether the reduction in calcium accumulation by cardiac mitochondria from diabetic rats is related to an enhanced susceptibility to induction of the mitochondrial permeability transition. Streptozotocin-induced diabetic rats were used as a model to study the alterations caused by diabetes in the permeability transition, 21 days after streptozotocin administration. Heart mitochondria were isolated to evaluate respiratory parameters and susceptibility to the calcium-dependent permeability transition. Our results show that streptozotocin diabetes facilitates the mitochondrial permeability transition in cardiac mitochondria, resulting in decreased mitochondrial calcium accumulation. We also observed that heart mitochondria from diabetic rats had depressed oxygen consumption during the phosphorylative state. The reduced mitochondrial calcium uptake observed in heart mitochondria from diabetic rats is related to an enhanced susceptibility to the permeability transition rather than to damage to the calcium uptake machinery.     

Adrenomedullin gene expression and peptide levels in the heart and blood vessels of streptozotocin-diabetic rats.

The aim of the present study was to assess the changes in gene expression and peptide adrenomedullin (AM) levels in cardiovascular and other tissues in the streptozotocin-diabetic rats. For this purpose, diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/Kg body weight). Half of the diabetic rats were subcutaneously injected with insulin in the afternoon (4 units/day) one week after STZ injection until the day before killing. Control rats received only saline injection. AM mRNA was determined in cardiovascular and other tissues of streptozotocin-diabetic rats using solution-hybridization-RNase protection assay. Circulating AM and peptide AM in cardiovascular and other tissues were estimated using a specific radioimmunoassay. There were increases in preproAM mRNA levels in the left and right ventricles and in the thoracic aorta in both the 2-week and 4-week diabetic rats, but not in the two atria, the mesenteric artery and the lung. In the 2-week diabetic rats, there were decreases in AM contents in the two atria and the lung but an increase in the thoracic aorta. In the 4-week diabetic rats, there were bigger decreases in the atria and also a decrease in the left ventricle. The plasma AM levels were not changed but there was an increase in the excretion of AM in the urine. Our results suggest a possible increase in AM release in the heart and the thoracic aorta in the 2-week and 4-week diabetic rats.     

Alterations of the plasma selenium concentrations and the activities of tissue peroxide metabolism enzymes in streptozotocin-induced diabetic rats

The activity of aortic glutathione peroxidase, a selenium-dependent enzyme, significantly decreased in rats 4 and 8 months after the injection of streptozotocin (STZ). Catalase activity was shown to occur at low levels in rat aorta and was not influenced by the diabetic state. Superoxide dismutase activity was less than detectable. The activity of selenium-dependent glutathione peroxidase in kidney, but not in lung and liver, increased in diabetic rats. Catalase and superoxide dismutase activities in the kidney were not altered. The plasma lipid peroxide value increased in diabetic rats. The selenium content in plasma of diabetic rats increased markedly while the increase in plasma glutathione peroxidase activities was insignificant. The observed abnormalities in plasma of STZ rats were improved by insulin treatment. The defects in glutathione peroxidase in the diabetic rat aorta were restored by insulin treatment. These results may suggest that the capacity of the antioxidative defense system in the aorta decreased in the diabetic state, and this may help clarify the mechanism of the pathogenesis of endothelial dysfunction associated with diabetes.     

Diabetes modulates differentially creatine kinase-specific activity responsiveness to estradiol-17beta and to raloxifene in rat organs

Diabetes mellitus increases the risk for CVD in women. While there is considerable evidence suggesting beneficial effects of estrogen on decreasing lipid peroxidation, atherosclerotic processes, and cardiovascular diseases, diabetes negates most estrogen protective effects as well as the skeletal protective effects of estrogens, which are not discernable in diabetic women. In the present study, we examined the in vivo effects of estradiol-17beta (E2), on creatine kinase (CK)-specific activity, in estrogen-responsive organs from healthy and diabetic rats. Healthy or diabetic (streptozotocin-induced) female rats were injected with either E2 (10-50 microg/rat) or raloxifene (Ral; 500-1,000 microg/rat). Twenty-four hours following the injection, animals were sacrificed; their organs removed and assayed for CK-specific activity. CK-specific activity in different organs [Left ventricle of heart (Lv), uterus (Ut), aorta (Ao), para uterine adipose tissue (Ad), epiphyseal cartilage (Ep), and diaphyseal bone (Di)] from healthy animals, was stimulated with increased doses of E2, with maximum at 20 microg/rat. Age-matched diabetic female rats exhibited a remarkable decreased response to E2 in all organs except Ut. In contrast, the response to Ral was not altered in diabetic rats. Similar results were observed in organs from ovariectomized female rats (Ovx), healthy or diabetic. These results support our previous in vitro findings, demonstrating that hyperglycemia decreases CK response to E2 but not to Ral in cultured human vascular and bone cells. In summary, diabetes mellitus decreases CK response to E2 but not that of Ral in skeletal and vascular tissues. The decreased response to E2 detected in organs derived from diabetic rats might be due to changes in nuclear and/or membrane estrogen receptors and/or other genomic and non-genomic pathways, as was shown in in vitro cellular models.     

Effect of exposure to diabetic and fasted plasma on glucose oxidation in rat aorta

Glucose metabolism is depressed in aortic intima-media of fasted and diabetic rats. The aim of this study was to elucidate the influence of diabetic and fasted plasma on glucose oxidation in rat aorta. Male Sprague-Dawley rats weighing about 200 g were used. Diabetes was induced by streptozotocin (65 mg/kg) and the rats were used after a diabetes duration of two weeks. Fasted rats were used after food deprivation for 3 days. Aortic intima-media was preincubated in plasma for 120 or 240 min. During a further incubation for 2 hours in Krebs-Henseleit bicarbonate buffer the oxidation of 14C-glucose to 14CO2 was measured. Preincubation of normal aorta in diabetic or fasted rat plasma and diabetic human plasma significantly depressed the subsequently determined glucose oxidation in comparison to aorta preincubated in normal plasma. Preincubation of aorta from diabetic or fasted rats in normal rat plasma enhanced the glucose oxidation compared with the glucose oxidation in aorta of diabetic or fasted rats after preincubation in the corresponding plasma. These results suggest that diabetic and fasted plasma contains factor(s) which in vitro depress glucose oxidation in vascular smooth muscle and, thus, may be of importance for the lowered glucose oxidation found in vascular smooth muscle preparations obtained from diabetic or fasted animals.     

Green tea impedes dyslipidemia, lipid peroxidation, protein glycation and ameliorates Ca2+ -ATPase and Na+/K+ -ATPase activity in the heart of streptozotocin-diabetic rats

Diabetes-induced hyperlipidemia, oxidative stress and protein glycation impair cellular calcium and sodium homeostasis associated with abnormal membrane-bound enzyme activities resulting in cardiac dysfunction in diabetes. To explore the cardioprotective mechanism of green tea in diabetes, we measured the changes in the levels of calcium, sodium, potassium and the activities of Na+/K+ -ATPase and Ca2+ -ATPase in green tea treated diabetic rat hearts. The effect of green tea on triglycerides, lipid peroxidation and protein glycation in diabetic heart were also measured to elucidate the underlying mechanisms. Diabetes was induced by streptozotocin (STZ, 60 mg/kg i.p.). Six weeks after the induction of diabetes, some of the diabetic rats were treated orally with green tea extract (GTE) (300 mg/kg/day) for 4 weeks. GTE produced reduction in blood glucose and lowered the levels of lipid peroxides, triglycerides and extent of protein glycation in the heart of diabetic rats. GTE blunted the rise in cardiac [Ca2+] and [Na+] whereas increased the activities of Ca2+ -ATPase and Na+/K+ -ATPase in diabetic rats. In conclusion, the data provide support to the therapeutic effect of GTE and suggest that a possible mechanism of action may be associated with the attenuation of the rise in [Ca2+] and [Na+] by ameliorating Ca2+ -ATPase and Na+/K+ -ATPase activities.     

BNP及NT-proBNP与2型糖尿病关系的研究进展

BNP及NT-proBNP是诊断心衰的重要指标。近年来BNP及NT-proBNP与2型糖尿病关系的研究有了新的进展。我们收集近年来国内外关于2型糖尿病中BNP及NT-proBNP的相关文献并进行研究。结果显示2型糖尿病合并冠心病、高血压、糖尿病肾病患者BNP或NT-proBNP有升高趋势。单纯2型糖尿病及糖尿病视网膜病变患者以及低血糖患者BNP或NT-proBNP差异无统计学意义。高血压、年龄、性别、体重指数、肾功能及心脏结构功能改变是2型糖尿病患者BNP及NT-proBNP的影响因素。降糖药物对2型糖尿病患者BNP及NT-proBNP水平的研究尚少,糖尿病病程、FPG以及HbA1c对BNP及NT-proBNP的影响尚存在争议。BNP及NT-proBNP升高对2型糖尿病合并冠心病、高血压、糖尿病肾病患者病情评估,预后判断及诊治具有非常重要的意义。降糖药物、糖尿病病程、FPG以及HbA1c对BNP及NT-proBNP的影响需要进一步研究。