ACTA ENDOCRINOLOGICA (BUC)

Context. MicroRNAs (miRNAs) are short noncoding RNAs involved in posttranscriptional regulation of gene expression that influence various cellular functions including glucose and lipid metabolism and adipocyte differentiation. Objective. The aim of this study was to evaluate the levels of miR-34a and miR-149 and their relationship with metabolic parameters in obese children and adolescents. Design. Seventy children and adolescents were enrolled in the study. Plasma levels of microRNAs were evaluated by real-time PCR using SYBR green and analyzed by ΔCt method. Plasma concentrations of visfatin and insulin were measured by ELISA method. Glucose and lipid profile were determined colorimetrically. HOMA-IR was calculated and used as an index of insulin resistance (IR). Results. miR-34a was significantly lower in subjects with insulin resistance compared to obese children with normal insulin sensitivity. There was an inverse relationship between miR-34a levels and both insulin and HOMA-IR. On the other hand, miR-149 was significantly correlated with visfatin. There was no significant difference in miR-34a and miR-149 between obese and normal weight subjects. Conclusions. miR-34a is associated with insulin and HOMA-IR and thus seems to be involved in IR. miR- 149 is inversely associated with visfatin levels which could be indicative of anti-inflammatory effect of this miRNA.

Background. This study aimed to assess the mechanism through which Wnt/ beta - catenin signaling pathway, and StarD7, prometes testosterone synthesis, and to explore a new pathway for the regulation of testosterone synthesis. Animals and Methods. Leydig cells were isolated from male Sprague-Dawley rats divided into four groups and treated with Annexin 5 in concentration of 0, 0.1, 1 and 10 nmol/L. Testosterone secretion, expression of StarD7, StarD7 mRNA, β-catenin and changes of β – catenin localization in Leydig cells of testis of rats were tested in the four groups. Results. mRNA and protein levels of StarD7 and β-catenin increased significantly, upon stimulation with 1 nmol/L annexin 5. Accumulation of β-catenin inside the cells and the nucleus, was observed by immunofluorescence staining, in cells treated with annexin 5. These findings indicate a possible role of StarD7 and β-catenin in the process of annexin5-mediated stimulation of testosterone synthesis. Conclusions. Wnt/β-catenin signaling pathway and StarD7 are involved in the process of annexin5 stimulation of testosterone synthesis. Activation of Wnt/ β-catenin signaling pathway by Annexin5, and increase in StarD7 expression lead to elevated expression of key regulatory enzymes in testosterone synthesis, thus promoting testosterone synthesis.

Gastrointestinal complaints are common among diabetic patients. The gastrointestinal tract contains melatonin. The binding sites of melatonin have been identified in all GIT tissues. Melatonin can modify activities of the gut and liver. The aim of this study was to evaluate the possible protective effects of melatonin against gastric motility and secretary responses in Streptozotocin-induced diabetes in rats. Methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. One week after inducing diabetes, Melatonin (5, 10, 20 mg/ kg/day, IP.) was injected for 14 days. Gastric acid and mucus were measured in all animals by chemical methods. Gastric motility was investigated by powerlab system. Results. Streptozotocin induced a significant increase in blood glucose levels (p<0.001) and significant decrease in gastric acid, mucus, motility and body weight in diabetic groups. Treatment of diabetic rats with melatonin significantly reduced blood glucose (p<0.001) and increased gastric mucus (p<0.001) and motility (p<0.01 and p<0.05 in groups 4 and 5 respectively) with no effect on body weight and gastric acid concentration. Conclusion. These data suggested that melatonin treatment has a therapeutic effect on diabetic gastrointestinal disturbances by reduction of serum glucose and increasing gastric motility and gastric mucus levels, but no effect on gastric acid and body weight.

The aim of this study was to examine the highglucose and high fatty acid status effect on the development of atherosclerosis. Materials and Methods. We used rat thoracic aorta smooth muscle cell line A7r5. We investigated mechanisms underlying high-glucose and high fatty acid (oleic acid) conditions on vascular smooth muscle cell (VSMC) mimicking concurrent status of diabetes and dyslipidemia. Results. Glucose-oleic acid stimulated cell proliferation and migration while the proliferating cell nuclear antigen (PCNA) level and matrix metalloproteinase (MMP)-2 were activated. In addition, the expressions of connective tissue growth factor (CTGF) and fatty acid synthase (FASN) enhanced by glucose-oleic acid were increased. The proliferation signal mediated by glucoseoleic acid condition was demonstrated via CTGF/FASN, while MMP-2 was regulated by CTGF but not FASN. Conclusion. Oleic acid in the presence of high glucose level can induce VSMC proliferation and migration leading to diabetes-associated vascular atherosclerosis. Furthermore, via activation of CTGF, increased expression of FASN suggested a possibility of lipogenesis in VSMC which may also contribute to diabetes-associated vascular atherosclerosis.

Objective. The aim of the study was to test whether a correlation exists between the Epworth Sleepiness Scale (ESS) and respiratory sleep parameters in patients with\r\ntype 2 diabetes.\r\nDesign. Subjects and Methods.The records of 83 consecutive patients (mean age 54.6? 9.8 years) with type 2 diabetes\r\nthat accepted to perform an in-hospital sleep study for screening of sleep apnea have been retrospectively evaluated.\r\nResults. There was a weak positive correlation between apnea/hypopnea index (AHI), oxygen desaturation index and ESS, and a weak negative correlation between ESS and mean O2 saturation. When data was separately analyzed in men and\r\nwomen, it could not be identified any correlation between sleep respiratory parameters and ESS in men. In women,\r\ncorrelation coefficients increased, proving a stronger relationship between ESS and AHI (r=0.65, p<0.001), mean O2 saturation (r=-0.52, p=0.005) and oxygen desaturation index (r=0.60, p=0.001). ESS had only a moderate level of accuracy in identifying patients with moderate and severe sleep\r\napnea (sensitivity 84.1%, specificity 74.1%, PPV 84.1%, NPV 74.1%). In women ESS showed a higher sensitivity than in men\r\n(92% vs. 80.6%), but a lower PPV (63% vs.78.1%) in predicting the presence of an AHI &#8805; 15.\r\nConclusions. In women with type 2 diabetes, it is possible to suspect the existence of SAS solely on the basis of the\r\nESS score. In male population, symptoms evaluated by questionnaires, such as the ESS, provide additional information which combined with clinical findings are helpful in selecting patients who are candidates for further detailed sleep studies.

Context. Hashimoto’s thyroiditis is the most common autoimmune disorder as cause of secondary hypothyroidism. The disease is associated with several metabolic disturbances and inflammatory disorders. Objectives. The aim of the current report was to evaluate several inflammatory and metabolic predictors of Hashimoto’s thyroiditis. Subjects and Methods. In the current study, forty patients with Hashimoto’s thyroiditis participated in the current study. They were aged between 20 to 50 years old. Anthropometric and nutritional measurements were assessed and biochemical factors including serum VEGF, IL-23, Nesfatin-1 and serum lipids were measured. Results. Waist circumference was higher among patients with lower serum TSH concentrations. Serum HDL and T4 concentrations were lower and serum IL-23 was higher among patients with higher TSH concentrations. BMI, WC and serum HDL were negative predictors of serum TSH while IL-23 was positively associated with TSH concentrations. Serum lipids including TC, TG and LDL were also negatively associated with T3 and T4 concentrations. Conclusions. According to our findings, VEGF and serum IL-23 were potent predictors of Hashimoto’s thyroiditis. However, further studies are warranted to better clarify these associations and underlying pathologic mechanisms.

Background. Lithium, a well known antimanic drug, has adverse effects on endocrine functions; but it is unknown in aged animals.\r\nAim. Untoward effects of lithium on thyroidal and extra-thyroidal thyroid hormones were investigated in adult and aged rats.\r\nMaterials and methods. Lithium was injected intraperitoneally at a dose of 2 mEq/kg\r\nbody weight daily to one group of rats for 10 days and the other for 25 days respectively. Thyroid and serum T3 and T4, and extrathyroidal liver and kidney T3and T4 levels were\r\nmeasured by ELISA. Pituitary and serum TSH-like substance was determined using a human-TSH immunoassay kit. Thyroperoxidase profile was measured spectrophotometrically.\r\nResults. Lithium decreased thyroid and serum T3 and T4 levels, and increased pituitary and serum TSH-like profiles after 10 and 25 days of treatments respectively in adult and aged rats. Thyroperoxidase activity was decreased in all the treatments of adult and aged rats. Liver\r\nand kidney T3 and T4 profiles were also decreased in lithium recipients. Lithium actions were severe after 10 days of treatment in adult rats and 25 days treatment in aged rats.\r\nConclusion. Lithium has untoward effects on thyroid and extra-thyroidal thyroid hormone synthesis irrespective of the age of rats.

Background. Hashimoto’s thyroiditis is in coexistence with many autoimmune disorders, especially celiac disease. There are a limited number of studies evaluating the prevalence of celiac-related antibodies in patients with Hashimoto’s thyroiditis. Objective. This study aimed to further investigate the prevalence of undiagnosed celiac disease in patients with Hashimoto’s thyroiditis and the relationship between these two autoimmune disorders in these patients Subjects and methods. This study was performed on 82 women aged 20-50 years including 40 patients with Hashimoto’s thyroiditis and 42 healthy age-matched individuals. Anthropometric assessments were performed and biochemical parameters including thyroid hormones (TSH, T3 and T4), antithyroid antibodies, anti-tissue transglutaminase and anti-gliadin antibodies were measured by enzyme linked immunosorbent assay (ELISA). Results. The prevalence of IgG and IgA anti-tissue transglutaminase antibodies and IgA anti-gliadin antibody was higher in Hashimoto’s thyroiditis patients compared with control group (15% vs. 7%, 22.5% vs. 17% and 15% vs. 12% respectively). In ordinal regression model, serum IgG anti-tissue transglutaminase and IgA anti-gliadin antibodies were significant predictors of antithyroid antibodies in patients with Hashimoto’s thyroiditis (P < 0.05). A significant relationship between serum TSH and IgG antigliadin antibody were also found (P = 0.003). Conclusion. To our findings, a high prevalence of anti-tissue transglutaminase and IgA anti-gliadin antibodies and their positive relationship with antithyroid antibodies in patients with Hashimoto’s thyroiditis were reported. These findings further warrant the need for interventions to reduce the prevalence of these antibodies in Hashimoto’s thyroiditis for preventing the occurrence of celiac disease in these patients.

Background. Erectile dysfunction(ED) in men is a frequent under-reported complication of diabetes mellitus, which is becoming significant health problem worldwide. Aims. The study aims to determine the prevalence and risk factors for development of ED in North Indian patients with type 2 diabetes mellitus. Methods. We used international index of erectile function (IIEF-5) for the assessment of ED in 796 patients with type 2 diabetes mellitus. We recorded the age, duration of diabetes, glycemic status, body mass index, diabetes medications, microvascular and macrovascular complications. Results. The mean age of patients in the study was 49.38 ± 9.52 years. The prevalence of ED in patients with type 2 diabetes mellitus was 79.4%. Logistic regression analysis revealed that age, body mass index, glycemic control, insulin therapy, retinopathy and nephropathy was not significantly associated with erectile dysfunction in patients with type 2 diabetes mellitus. Duration of diabetes (OR = 1.054, 95% CI 1.007 to 1.102, P=0.023) and vibration perception threshold (OR = 1.071, 95% CI 1.042 to 1.102, P=0.000) were identified as key risk factors for development of ED. Conclusion. Duration of diabetes and peripheral neuropathy emerged as significant risk factors for development of severe erectile dysfunction.

Context. Betel nut is consumed by millions of people for stress reduction and increased capacity to work. One of its components is arecoline which is useful for Alzheimer and schizophrenia; it also influences endocrine and gonadal functions. Objective. Objective is to examine whether arecoline can influence pineal-testicular function in metabolic stress. Design. Rats were deprived of food or water or treated them with arecoline, each separately for 5 days. Subjects. Pineal and testis with sex accessories were studied. Methods. Ultrastructural (pineal, testis, Leydig cells and prostate), hormonal (melatonin and testosterone) and other parameters (fructose and sialic acid) were examined. Pineal indoleamines were quantitated by fluorometric method; testosterone by ELISA, and carbohydrate fractions by spectrophotometric methods. Results. Inanition/ water deprivation caused pineal stimulation ultrastructurally (with enlarged synaptic ribbons) and elevation of melatonin level, but reproductive dysfunction by ultrastructural degeneration of Leydig cells and prostate with fall of testosterone, fructose and sialic acid concentrations. Arecoline treatment showed reversed changes to those of metabolic stress, but arecoline treatment in metabolic stress showed same results as in metabolic stress. Conclusion. The findings suggest that arecoline cannot alter the action of metabolic stress on pineal-testicular activity in rats.