ACTA ENDOCRINOLOGICA (BUC)

Background. Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. Method. Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). Results. After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol- 3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3- phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)- like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. Conclusion. Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

Background. Composite adrenal pheochromocytoma-ganglioneuromas (PHEO-GNs) are well-defined neoplasms of the adrenal medulla, consisting of both endocrine and neural components. They are extremely rare. To date, only 46 cases have been reported in the English literature. Case report. We describe an adult case of endocrinologically active adrenal composite PHEO-GN diagnosed in a 62-year-old male patient with history of dizziness, headache, nausea, vomiting, and uncontrolled hypertension including intermittant hypertension attacks. On physical examination, he had a blood pressure (BP) of 170/110 mmHg. 18-fluorodeoxyglucose positron emission tomography-computed tomography showed a right adrenal tumor with increased metabolic activity. Urinary levels of catecholamines and their metabolites were prominently elevated. Right adrenalectomy was performed for treatment purposes. The histological diagnosis of the resected tumor was composite adrenal PHEO-GN. Conclusions. Composite adrenal PHEO-GN is a rare entity and preoperative diagnosis is difficult. Its hormonal activity and imaging characteristics are frequently very similar to those of other adrenal tumors, especially pure PHEO and adrenal carcinoma. Therefore, careful evaluation by endocrine tests and multiple imaging procedures are needed for providing a differential diagnosis. However, definitive diagnosis composite adrenal PHEO-GN is established by histological and immunochemical studies. To our knowledge, the present case is the first report that describes composite adrenal PHEO-GN in a patient from Turkey. We discuss this case and review the literature on this unusual entity.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Context. Visceral adipose tissue (VAT) is a strong predictor of carbohydrate metabolism disorders. Abdominal bioelectrical impedance analysis (A-BIA) is a simple method for the measurement of VAT and is a promising tool in screening and follow-up of abdominal obesity. However the role of A-BIA in dieting individuals has not been evaluated adequately in longitudinal followup studies. Objective. The aim of this study is to determine the role of A-BIA in identifying the changes in metabolic predictors after diet and/or exercise therapy. Design. All patients who sought weight loss treatment underwent baseline assessment and were prescribed a program of diet. After a mean follow-up of 3.2 months, data were analyzed. Subjects and Methods. Ultimately, 103 participants who reported adhering to the diet, enrolled to the study. We tested associations between changes in body composition measures and changes in laboratory measures using correlations and multivariate linear regression analysis. Results. Mean loss of body weight was 3.4±2.8 kg. All but waist-to-hip ratio, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels changed significantly (p<0.001). Decreases in body weight, body mass index (BMI), and VAT level significantly correlated with decreases in fasting blood glucose, fasting insulin level, and HOMA-IR score (r=0.230–0.371). In multiple linear regression analysis changes in BMI and VAT significantly correlated with change in HOMA-IR score (F(7.93)=2.283, p=0.034, R2=0.147). Conclusion. Decreases in BMI and VAT, as determined by A-BIA, were predictors of changes in metabolic laboratory measures. A-BIA is useful for followup of patients receiving diet therapy for weight loss.

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.