Iranian Journal of

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Background: The precise mechanisms of vascular diseases in insulin dependent diabetes mellitus (IDDM) are not clearly understood. There are evidences of alteration in mechanisms involved in regulating vascular tone including increased ACE activity in some tissues. To investigate the effect of insulin treatment on these changes this study was performed.
Methods: Three groups of 8 male Sprauge Dawely rats including control (C) and two diabetic groups (D, IT) were used in this study. Diabetes was induced by injection of 60 mg/kg STZ ip. After induction of diabetes IT group were treated with insulin (10 units/kg/day s.c.) for four weeks. The control group and the untreated diabetic group were treated with the same amount of Saline and for the same time. ACE activity was determined by HPLC method.
Results: 4 weeks after induction of diabetes, SBP and ACE activity in serum, lung, heart and aorta increased in D group compared to control rats. Insulin treatment reversed these changes to normal values in IT group.
Conclusion: It is concluded that increased ACE activity could contribute to the development of diabetic vasculopathy and ACE reducing activity of insulin may be partially involved in decrease of cardiovascular complications in diabetes.

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Background: Due to homeostatic and regulatory potentials of nitric oxide (NO) in vascular physiology, regulatory systems that determine NO bio-synthesis and bioavailability have been the subject of extensive research in molecular medicine. In the field of vascular system pathophysiology, endothelial nitric oxide synthase (eNOS) which is the major producer and regulator of NO in vascular tissues has received the most attention. Impairment of NO bioavailability (NO quenching) is a common feature in poorly controlled diabetics due to increased catabolism and decreased production of NO. Such impairment in severe forms could end to vasodilation breakdown in peripheral tissues (mainly in skeletal muscles) and defective regional blood flow, that in turn disturb insulin-dependent glucose uptake ensuing insulin resistance state.
Methods: The phenotypic impact of an eNOS gene polymorphism at position 786*C/T (that its functionality has been revealed already) on genetic propensity to diabetic retinopathy is evaluated in a British-Caucasian population with type 1 diabetes (T1DM).
Results: In contrast to genotypes, there was a significant difference in distribution of allele frequencies between T1DM patients (n= 249) and healthy controls (n= 104) (p= 0/036), that may imply eNOS and/or NO involvement in development of T1DM. Most notably a significant difference also was evident in allele frequency between retinopaths (n= 134) and healthy controls (p= 0/02). No significant difference was detected when the genotype/allele frequencies were compared between retinopaths (n= 134) and non-retinopaths diabetics (n= 115) (p=NS).
Conclusion: Our data is compatible with previous studies which demonstrated that allele C of eNOS 786*C/T polymorphism is associated with increased HbA1c levels. By emphasizing the phenotypic and prognostic value of the abovementioned polymorphism, our data calls for further investigations to find out whether this polymorphism can be employed as a genetic marker in clinical medicine to recognize high-risk diabetics at the time of diabetes onset/diagnosis.

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Background: Sulfonylurea agents such as Glibenclamide (Glyburide) have been widely prescribe in treatment of type 2 diabetic patients for decades, but controversy remains about their precise mechanism of action. On the other hand, glucokinase serves as a glucose sensor in pancreatic β-cells and plays a key role in the regulation of insulin secretion and glucose homeostasis. The aim of the present study was to evaluate the effect of Glibenclamide on insulin secretion and glucokinase activity in the rat isolated pancreatic islets of Langerhans.
Methods: The islets from normal and type 2 diabetic rats were isolated by collagenase digestion method. Glucokinase activity was measured via determination the rate of glucose-6-phosphate formation in the fluorometric assay. Insulin secretion from hand-picked islets was evaluated by static incubation technique. Insulin concentration was measured by rat insulin ELISA kit.
Results: Our findings obtained from incubation of Glybenclamide with pancreatic islets revealed that this agent increases basal insulin secretion (at 2.8 mM glucose) in both normal and diabetic rats as compared it with control islet (without drug). However, the increase of insulin secretion in response to 16.7 mM glucose was not significant. On the other hand, Glybenclamide had no activating and/or inhibiting effect on pancreatic glucokinase activity in both diabetic and normal Rats. But reduced activity of this enzyme in diabetic rats was significant in comparison with normal.
Conclusion: These data show that increasing effect of Glybenclamide on insulin secretion is through a mechanism other than affecting Glucose Mediated Insulin Release. Moreover, the regulation of pancreatic glucokinase does not depend on glybenclamid.

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Background: The purpose of this study was to evaluate the effect of six weeks of endurance training with sour lemon consumption on plasma levels of endolin-1 and nitric oxide in streptozotocin-induced diabetic rats.
Methods: In this experimental study, 72 male Wistar rats (Weight; 200 ± 12 g) were selected and randomly divided into eight groups after becoming diabetic. Endurance training protocol was performed on rats for 6 weeks. Lemon essential oil (50 mg/kg) was administered using gavage. Plasma endolin-1 levels were measured by ELISA and serum nitrite levels were measured as a major metabolite of nitric oxide. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis.
Results: The results showed that the mean levels of endothelin-1 in the endurance training + lemon group and diabetes + endurance training + lemon were significantly lower than the control group (p<0.05). Also, the mean nitric oxide levels in the diabetes + lemon group were significantly lower compared to the control group, but in the endurance + lemon training group and the diabetes + endurance training + lemon group was significantly higher than the control group (p<0.05).
Conclusion: According to the results of this study, it can be concluded that endurance training with consumption of lemon may improve endothelial function and vascular occlusion in diabetic patients by reducing the concentration of endothelin-1 levels and increasing nitric oxide levels.

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Background: The apoptosis process as a common status in heart injuries could be imposed significantly by hyperglycemia chronically. Therefore, the aim of this study was to investigate the inhibitory effects of concurrent training and antioxidant supplementation individually and in combination on biogenesis and function of mitochondrial in the heart tissue of diabetic rats with STZ.
Methods: In this experimental study, fifty male Sprague Dawley rats were classified into five groups (n=10 each group): healthy rats as control, diabetic rats, diabetic combined resistance/endurance training, diabetic rats which consumed supplementation vitamin E and C, and the combined supplementation and training. Here, we calculated changes in genes expression based on artificial intelligence methods and evaluated genes expression in apoptotic influencing combined training and antioxidants vitamins consumption in heart injured models by streptozotocin via Real-Time PCR. Combination training including, respectively, resistance training, 5 days a week with increasing intensity of 5-45% of rat weight and endurance training on treadmill increasingly from 10-30 minutes and intensity of 40-75% of maximum speed during 8 weeks. Data were analyzed by two-way ANOVA (P<0.05).
Results: the relative expression of PGC1α and Tfam were significantly decreased between healthy control and diabetes controls group. The results indicated that significantly increased of PGC1α and Tfam in the training(P<0.05), supplement(P<0.05) and combination groups(p<0.05). In addition, in this study, it was observed that supplementation and exercise had an increasing effect on the expression of PGC1α and Tfam genes. On the other hand, glucose concentration and weight of rats treated with supplementation and exercise were significantly reduced compared to other groups (P<0.05).
Conclusion: Based on the results, interaction between antioxidant supplements and exercise reduced the glucose concentration and improved the mitochondrial biogenesis of heart tissue, while the combination of these two interventions compared to the effect of each alone, the effect has more.