The anti-inflammatory effect of omega-3 polyunsaturated fatty acids dramatically decreases by iron in the hippocampus of diabetic rats.

AIMS: Receptor for advanced glycation end products (RAGE) production is induced by diabetes. Microglial cells are activated by RAGE and produce inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and oxidative stress markers. Persistent production of TNF-α can provide a link between diabetes and Alzheimer's disease (AD). The purpose of this study was to investigate the effect of concomitant use of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) with iron supplements on microglial cell activation and inflammatory conditions in the hippocampus of type 2 diabetic rats. MAIN METHODS: Diabetic and normal Wistar rats were divided into six groups. Oxidative stress markers (total oxidant status (TOS), total antioxidant capacity (TAC), and malondialdehyde (MDA)), mRNA expression and protein levels of RAGE and TNF-α were evaluated in the hippocampus of the controls and supplemented with ferrous sulfate and ω-3 PUFAs alone and together rats. Also, the entry of microglia cells into the hippocampus was evaluated by immunohistochemistry technique. KEY FINDINGS: Levels of the microglial activation (2.4 fold, p < 0.0001), MDA (84%, p < 0.0001) and oxidative stress index (OSI) (11%, p = 0.0094), mRNA expression and protein contents of RAGE (1.83 fold and 82% respectively) and TNF-α (2.25 fold and 86% respectively) were strongly influenced by negative effect of iron compared to the group receiving only ω-3 PUFAs which was dramatically improved by vitamin E. SIGNIFICANCE: These observations indicated that the co-supplementation of ferrous sulfate with ω-3 PUFAs decreases the anti-inflammatory ability of ω-3 PUFAs in the hippocampus of diabetic rats via RAGE/TNF-α-induced oxidative stress pathway up-regulation.

Antihyperglycemic Effect of Rosa Damascena is Mediated by PPAR.γ Gene Expression in Animal Model of Insulin Resistance.

Insulin resistance is a condition in which insulin signaling and action are impaired in insulin sensitive tissues and result in hyperglycemia, hyperlipidemia, and type 2 diabetes mellitus. Our previous studies have shown that Rosa damascena has antihyperglycemic effects on diabetic and normal rats. Therefore, we conducted a study to evaluate the effect of this medicinal plant on insulin sensitivity in rats. This study was performed on high fructose diet insulin resistant rats and pioglitazone, an insulin sensitizing drug, was used as a positive control. Insulin resistance was developed in animals by high fructose diet within six weeks. Then, Rosa damascena extract and pioglitazone were administered by gavage for two weeks and results were compared with two control groups. After treatment period, serum glucose, insulin, adiponectin, triglyceride, and cholesterol were assayed in fasting state. Plasma free fatty acid profile was analyzed by GC. Liver PPAR.γ and muscle GLUT.4 gene expressions were assessed by real time PCR and western blotting. Animals were treated with rosa damascena extract showed levels of insulin (42 ± 2.7 pmol/L). adiponectin (5.6±0.17 µg/mL). glucose (129±4.7 mg/dL). and triglyceride (75 ± 9 mg/dl) which were significantly improved as compared with control group insulin (137 ± 34 pmol/L), adiponectin (3.9±0.15 µg/mL). glucose (187±15 mg/dL). and triglycerides (217±18 mg/dL). PPARγ protein level was also significantly increased in Rosa damascene treated group. Our results demonstrated that rosa damascena extract has useful effects on insulin resistant animals and by increasing insulin sensitivity can be considered as a potential agent in control of diabetes.

Berberis integerrima ameliorates insulin resistance in high- fructose-fed insulin-resistant rats.

OBJECTIVES: This study was aimed to investigate the effect of Berberis integerrima (B. integerrima) extract on insulin sensitivity in high-fructose-fed insulin-resistant rats. MATERIALS AND METHODS: Experimental rats were randomly divided into two groups: the control group was fed a regular chow diet while other group fed with a high-fructose diet for 8 weeks. After the first six weeks, the animals were treated with B. integerrima extract or pioglitazone for two weeks. Insulin and adiponectin levels were measured by ELISA. Additionally, Insulin resistance was calculated using a Homeostasis Model Assessment of Insulin resistance (HOMA-IR). The plasma free fatty acid (FFA) profile was obtained by gas chromatography. PPARγ and GLUT4 gene expression were assessed by real-time polymerase chain reaction (PCR) and western-blotting. RESULTS: Comparing the B. integerrima treated group with the control group, weight gain (P=0.009) and levels of insulin (P=0.001), blood glucose (P<0.0001), and HOMA-IR (P<0.0001) were significantly reduced. Additionally, the adiponectin concentration was significantly increased (P<0.0001). Among the FFA fractions, the mean concentration of palmitoleic acid and stearic acid in the B. integerrima group were significantly higher than the control group (P<0.0001 and P=0.005, respectively). However, there was no significant difference at the mRNA and protein level of GLUT4 and PPAR-γ between B. integerrima treated group and control group. CONCLUSION: The study findings revealed that B. integerrima might be a protective candidate against Type 2 diabetes/insulin resistance through direct insulin-like effect and an increase in adiponectin levels. However, the mechanism of B. integerrima was independent of GLUT4 and PPARγ.

Trigonella foenum-graecum water extract improves insulin sensitivity and stimulates PPAR and γ gene expression in high fructose-fed insulin-resistant rats.

BACKGROUND: Insulin resistance is the main defect associated with the metabolic syndrome. In obesity, the decreased adiponectin levels and elevation of plasma-free fatty acids are the main factors associated with insulin resistance. In this study, we evaluated the effect of trigonella foenum-graecum (TFG) extract on insulin sensitivity in high fructose-fed insulin-resistant rats. MATERIALS AND METHODS: Experimental rats were fed with a high fructose diet for eight weeks. After the first six weeks, the animals were treated with trigonella foenum-graecum extract or pioglitazone for two weeks. Serum glucose, triglycerides, cholesterol, and HDL-c were measured. The insulin and adiponectin levels were assayed by the enzyme-linked immunosorbent assay (ELISA), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. The plasma-free fatty acid profile was obtained by gas chromatography. PPARγ and GLUT4 gene expression were assessed by real-time polymerase chain reaction (PCR) and western blotting. RESULTS: In the trigonella foenum-graecum- extract treated group the following results were obtained: Insulin (49.02 ± 6.93 pmol/L), adiponectin (7.1 ± 0.64 µg/ml), and triglycerides (110.3 ± 16.7 mg/dl), which were significantly different and improved compared to the control group (insulin (137 ± 34 pmol/l), adiponectin (3.9 ± 0.15 µg/ml), glucose (187 ± 15 mg/dl), and triglycerides (217 ± 18 mg/dl). Also the PPARγ gene expression was significantly increased compared to the control group. CONCLUSION: This study demonstrates the beneficial effects of trigonella foenum-graecum extract on insulin resistance in rats fed on a high-fructose diet. At least three mechanisms are involved, including direct insulin-like effect, increase in adiponectin levels, and PPARγ protein expression.

Protective effects of an interaction between vagus nerve and melatonin on gastric ischemia/reperfusion: the role of oxidative stress.

OBJECTIVES: Vagal pathways in gastrointestinal tract are the most important pathways that regulate ischemia/reperfusion (I/R). Gastrointestinal tract is one of the important sources of melatonin production. The aim of this study was to investigate probable protective effect of the interaction between vagus nerve and melatonin after I/R. MATERIALS AND METHODS: This study was performed in male rats that were divided into six groups. Cervical vagus nerve was cut bilaterally after induction of I/R and the right one was stimulated by stimulator. Melatonin or vehicle was injected intraperitoneally. The stomach was removed for histopathological and biochemical investigations. RESULTS: A significant decrease in infiltration of gastric neutrophils and malondialdehyde (MDA) level after I/R was induced by melatonin and was disappeared after vagotomy. The stimulation of vagus nerve significantly enhanced these effects of melatonin. However, a stimulation of vagus nerve alone increased neutrophils infiltration and MDA level. Melatonin significantly increased the activities of catalase, glutathione peroxidase (GPx), superoxide dismutases (SOD). Unlike stimulation of vagus nerve, vagotomy decreased these effects of melatonin. CONCLUSION: According to these results, it is probable that protective effects of melatonin after I/R may be mediated by vagus nerve. Therefore, there is an interaction between melatonin and vagus nerve in their protective effects.

Evaluation of Salivary Secretory Immunoglobulin A Levels in Diabetic Patients and Association with Oral and Dental Manifestations.

OBJECTIVES: Oral and dental manifestations in diabetic patients can arise due to numerous factors, including elevated salivary secretory immunoglobulin A (s-IgA) levels. This study aimed to evaluate s-IgA concentrations in patients with type 2 diabetes mellitus (T2DM) and to investigate the association between s-IgA levels and oral and dental manifestations of T2DM. METHODS: This cross-sectional descriptive study was carried out between October 2011 and September 2012 in Kerman, Iran, and included 260 subjects (128 patients with T2DM and 132 healthy controls). Unstimulated salivary samples were collected from all subjects and s-IgA levels were determined using the immunoturbidimetric method. The oral cavities and teeth of T2DM patients were evaluated for oral and dental manifestations. RESULTS: Both diabetic and control subjects with higher concentrations of s-IgA had significantly higher numbers of decayed, missing or filled teeth (DMFT) and periodontal index (PDI) scores (P <0.050). s-IgA levels were significantly higher in subjects with oral candidiasis (P <0.050). Among diabetic patients, significantly higher s-IgA levels were concomitant with xerostomia and denture stomatitis (P ≤0.050). There were no significant differences between s-IgA concentrations and other oral or dental manifestations in either group. CONCLUSION: Individuals with a greater number of DMFT, a higher PDI score and oral candidiasis had significantly higher s-IgA levels. s-IgA levels were not significantly higher among diabetic patients in comparison to the control group. However, significantly higher s-IgA levels occurred with xerostomia and denture stomatitis in diabetic patients. In addition, s-IgA was significantly higher in patients with uncontrolled diabetes compared to those with controlled diabetes.

Plasma cystatin-C and risk of developing gestational diabetes mellitus.

AIMS: Cystatin-C, a low molecular weight protein, is effectively applied to evaluate the risk of developing renal insufficiency, cardiovascular disorders, neural defects, and inflammatory states. However, the role of this biomarker to monitor different pregnancy-related complications remains controversial. MATERIALS AND METHODS: In the present study, we compared serum cystatin-C concentration between pregnant women with gestational diabetes mellitus (GDM) and healthy pregnant women to assess value of this biomarker to predict presence of GDM in these women. The study consisted of 60 consecutive pregnant women (30 women suffered GDM and 30 healthy pregnant women) enrolled in Afzalipour hospital in Kerman, Iran in 2012. Fasting blood sample was collected to perform measurements on plasma glucose, lipids, serum creatinine, and C-cystatin. Serum cystatin-C level was quantified using ELISA techniques. RESULTS: Unadjusted comparison of cystatin-C level between the two study group showed no significant discrepancy between them so that the level of this biomarker in GDM group was 593.00±204.81 mg/L and in healthy group was 531.67±87.52 mg/L (P=0.137); while in multivariable linear model with the presence of associated variables, GDM was a main determinant for increased level of cystatin-C (standardized beta of 0.355, P-value of 0.014). CONCLUSION: Gestational age was also identified to be another indicator of elevated cystatin-C. In final, our study showed that cystatin-C can be a reliable, useful and promising marker of GDM appearance in pregnant women.

Relationship between serum cystatin C and polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) causes an increased risk of metabolic cardiovascular syndrome. Also, cystatin C serum levels are associated with the risk of cardiovascular events in metabolic syndrome patients. OBJECTIVE: To investigate the relationship between cystatin C in PCOS patients. MATERIALS AND METHODS: 35 women with PCOS were compared to 35 women with healthy matched age and body mass index. They all underwent tests to determine plasma levels of C-reactive protein (CRP), cystatin C, lipid profile and apo-lipoprotein. Blood pressure and demographic variables of each subject were obtained. RESULTS: Systolic and diastolic blood pressure were higher in PCOS patients compared to control group. Triglyceride and low-density lipoprotein cholesterol levels were higher in PCOS; contrariwise, high-density lipoprotein was lower from that of healthy volunteers. Cystatin and CRP levels were significantly higher in patients with PCOS in comparison with healthy subjects (p<0.0001). Among measured determinants, only PCOS status was independently associated with cystatin C. CONCLUSION: Cystatin C was positively correlated with PCOS status concentrations but not with systolic and diastolic blood pressure, or any of the lipid profile variables or demographic characteristics. Indeed, no correlation was found between cystatin C and CRP levels. Therefore, cystatin C might be related to PCOS beyond its use as a marker of the renal function.