BioMed Research International: Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Liraglutide Suppresses Obesity and Hyperglycemia Associated with Increases in Hepatic Fibroblast Growth Factor 21 Production in KKAy Mice Mon, 07 Apr 2014 10:03:42 +0000 Social isolation contributes to the development of obesity and insulin-independent diabetes in KK mice. Here we show that systemic administration of liraglutide, a long-acting human glucagon-like peptide-1 (GLP-1) analog, significantly decreased food intake, body weight, and blood glucose levels at 24 h after its administration while having no significant effects on plasma insulin and glucagon levels in individually housed KK mice. In addition, the systemic administration of liraglutide significantly increased plasma fibroblast growth factor (Fgf) 21 levels (1.8-fold increase) associated with increases in the expression of hepatic Fgf21 (1.9-fold increase) and Ppar (1.8-fold increase), while having no effects on the expression of hepatic Ppar and Fgf21 in white adipose tissue. Moreover, systemic administration of liraglutide over 3 days significantly suppressed food intake, body weight gain, and hyperglycemia in KK mice. On the other hand, despite remarkably increased plasma active GLP-1 levels (4.2-fold increase), the ingestion of alogliptin, a selective dipeptidyl peptidase-4 inhibitor, over 3 days had no effects on food intake, body weight, blood glucose levels, and plasma Fgf21 levels in KK mice. These findings suggest that systemic administration of liraglutide induces hepatic Fgf21 production and suppresses the social isolation-induced obesity and diabetes independently of insulin, glucagon, and active GLP-1 in KK mice. Katsunori Nonogaki, Miki Hazama, and Noriko Satoh Copyright © 2014 Katsunori Nonogaki et al. All rights reserved. Obesity and Headache/Migraine: The Importance of Weight Reduction through Lifestyle Modifications Thu, 03 Apr 2014 12:47:47 +0000 The aim of this study is to determine a possible relationship between prevalence, frequency, and severity of migraine and obesity. All pertinent data from the literature have been critically examined and reviewed in order to assess the possible relationship between obesity and migraine, in particular migraine frequency and disability in children, as well as in adult population studies. Prevalence, frequency, and severity of migraine appear to increase in relation to the body mass index, although this evidence is not supported by all the studies examined. Data from literature suggest that obesity can be linked with migraine prevalence, frequency, and disability both in pediatric and adult subjects. These data have important clinical implications and suggest that clinicians should have a special interest for weight reduction of obese children suffering from migraine, prescribing and supporting intensive lifestyle modifications (dietary, physical activities, and behavioral) for the patient and the entire family. Alberto Verrotti, Alessia Di Fonzo, Laura Penta, Sergio Agostinelli, and Pasquale Parisi Copyright © 2014 Alberto Verrotti et al. All rights reserved. NMR-Based Metabolomic Profiling of Overweight Adolescents: An Elucidation of the Effects of Inter-/Intraindividual Differences, Gender, and Pubertal Development Thu, 27 Mar 2014 16:31:18 +0000 The plasma and urine metabolome of 192 overweight 12–15-year-old adolescents (BMI of 25.4 ± 2.3 kg/m2) were examined in order to elucidate gender, pubertal development measured as Tanner stage, physical activity measured as number of steps taken daily, and intra-/interindividual differences affecting the metabolome detected by proton NMR spectroscopy. Higher urinary excretion of citrate, creatinine, hippurate, and phenylacetylglutamine and higher plasma level of phosphatidylcholine and unsaturated lipid were found for girls compared with boys. The results suggest that gender differences in the metabolome are being commenced already in childhood. The relationship between Tanner stage and the metabolome showed that pubertal development stage was positively related to urinary creatinine excretion and negatively related to urinary citrate content. No relations between physical activity and the metabolome could be identified. The present study for the first time provides comprehensive information about associations between the metabolome and gender, pubertal development, and physical activity in overweight adolescents, which is an important subject group to approach in the prevention of obesity and life-style related diseases. While this study is preliminary, these results may have the potential to translate into clinical applicability upon further investigations; if biomarkers for Tanner stage can be established, these might be used for identification of individuals susceptible to an early pubertal development. Hong Zheng, Christian C. Yde, Karina Arnberg, Christian Mølgaard, Kim F. Michaelsen, Anni Larnkjær, and Hanne C. Bertram Copyright © 2014 Hong Zheng et al. All rights reserved. Functional Analyses of c.2268dup in Thyroid Peroxidase Gene Associated with Goitrous Congenital Hypothyroidism Mon, 17 Mar 2014 13:52:45 +0000 The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a founder mutation in Taiwanese patients with dyshormonogenetic congenital hypothyroidism (CH). The functional impact of the mutation is not well documented. In this study, homozygous c.2268dup mutation was detected in two Malaysian-Chinese sisters with goitrous CH. Normal and alternatively spliced TPO mRNA transcripts were present in thyroid tissues of the two sisters. The abnormal transcript contained 34 nucleotides originating from intron 12. The c.2268dup is predicted to generate a premature termination codon (PTC) at position 757 (p.Glu757X). Instead of restoring the normal reading frame, the alternatively spliced transcript has led to another stop codon at position 740 (p.Asp739ValfsX740). The two PTCs are located at 116 and 201 nucleotides upstream of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated mRNA decay (NMD). Quantitative RT-PCR revealed an abundance of unidentified transcripts believed to be associated with the NMD. TPO enzyme activity was not detected in both patients, even though a faint TPO band of about 80 kD was present. In conclusion, the c.2268dup mutation leads to the formation of normal and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO enzymatic activity in Malaysian-Chinese patients with goitrous CH. Ching Chin Lee, Fatimah Harun, Muhammad Yazid Jalaludin, Chor Yin Lim, Khoon Leong Ng, and Sarni Mat Junit Copyright © 2014 Ching Chin Lee et al. All rights reserved. Estrogen Deficiency and the Origin of Obesity during Menopause Thu, 06 Mar 2014 09:25:08 +0000 Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the importance of estrogens in the development of metabolic diseases during menopause is disputed. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances of this metabolic signal lead to the development of metabolic syndrome and a higher cardiovascular risk in women. The absence of estrogens is a clue factor in the onset of cardiovascular disease during the menopausal period, which is characterized by lipid profile variations and predominant abdominal fat accumulation. However, influence of the absence of these hormones and its relationship to higher obesity in women during menopause are not clear. This systematic review discusses of the role of estrogens and estrogen receptors in adipocyte differentiation, and its control by the central nervous systemn and the possible role of estrogen-like compounds and endocrine disruptors chemicals are discussed. Finally, the interaction between the decrease in estrogen secretion and the prevalence of obesity in menopausal women is examined. We will consider if the absence of estrogens have a significant effect of obesity in menopausal women. Fernando Lizcano and Guillermo Guzmán Copyright © 2014 Fernando Lizcano and Guillermo Guzmán. All rights reserved. Inhibition of Ceramide De Novo Synthesis with Myriocin Affects Lipid Metabolism in the Liver of Rats with Streptozotocin-Induced Type 1 Diabetes Wed, 19 Feb 2014 10:09:28 +0000 Nowadays diabetes is one of the most common metabolic diseases. Sphingolipids, which are vitally important constituents of intracellular signal transduction pathways, may be among the most pathogenic lipid moieties intermingled in the origin and development of diabetes. It is now well established that inhibition of de novo ceramide synthesis with myriocin exerts positive effects on lipid metabolism and glucose homeostasis in type 2 diabetes mellitus animal models. However, its influence on type I diabetes still remains unknown. Therefore, the scope of this paper is to fulfill that particular gap in our knowledge. Krzysztof Kurek, Patrycja Wiesiołek-Kurek, Dominika M. Piotrowska, Bartłomiej Łukaszuk, Adrian Chabowski, and Małgorzata Żendzian-Piotrowska Copyright © 2014 Krzysztof Kurek et al. All rights reserved. Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance Tue, 04 Feb 2014 08:00:31 +0000 In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) () were compared with subjects with impaired glucose tolerance (IGT) (). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower () and HSP90 was 380% higher () in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research. M. Venojärvi, A. Korkmaz, S. Aunola, K. Hällsten, K. Virtanen, J. Marniemi, J.-P. Halonen, O. Hänninen, P. Nuutila, and M. Atalay Copyright © 2014 M. Venojärvi et al. All rights reserved. Plasma miR-126 Is a Potential Biomarker for Early Prediction of Type 2 Diabetes Mellitus in Susceptible Individuals Wed, 25 Dec 2013 17:03:50 +0000 Type 2 diabetes mellitus (T2DM) is a major public health problem in China. Diagnostic markers are urgently needed to identify individuals at risk of developing T2DM and encourage them to adapt to a healthier life style. Circulating miRNAs present important sources of noninvasive biomarkers of various diseases. Recently, a novel plasma microRNA signature was identified in T2DM. Here, we evaluated the T2DM-related miRNA signature in plasma of three study groups: normal (fasting glucose (FG), 4.8–5.2 mmol/L), T2DM-susceptible (FG, 6.1–6.9 mmol/L), and T2DM individuals (FG, ≥7.0 mmol/L) and tested the feasibility of using circulating miRNAs to identify individuals at risk of developing T2DM. Among the 5 miRNAs included in the signature, miR-29b and miR-28-3p are not detectable. miR-15a and miR-223 have comparable expression levels among three groups. Notably, miR-126 is the only miRNA that showed significantly reduced expression in susceptible individuals and T2DM patients compared to normal individuals, suggesting that miR-126 in circulation may serve as a potential biomarker for early identification of susceptible individuals to T2DM. Tao Zhang, Chunfang Lv, Liling Li, Sihan Chen, Shenglin Liu, Changyi Wang, and Bing Su Copyright © 2013 Tao Zhang et al. All rights reserved. Resistance Training for Diabetes Prevention and Therapy: Experimental Findings and Molecular Mechanisms Sun, 22 Dec 2013 11:54:47 +0000 Type 2 diabetes mellitus (T2D) is characterized by insulin resistance, impaired glycogen synthesis, lipid accumulation, and impaired mitochondrial function. Exercise training has received increasing recognition as a cornerstone in the prevention and treatment of T2D. Emerging research suggests that resistance training (RT) has the power to combat metabolic dysfunction in patients with T2D and seems to be an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. However, there is limited mechanistic insight into how these adaptations occur. This review provides an overview of the intervention data on the impact of RT on glucose metabolism. In addition, the molecular mechanisms that lead to adaptation in skeletal muscle in response to RT and that are associated with possible beneficial metabolic responses are discussed. Some of the beneficial adaptations exerted by RT include increased GLUT4 translocation in skeletal muscle, increased insulin sensitivity and hence restored metabolic flexibility. Increased energy expenditure and excess postexercise oxygen consumption in response to RT may be other beneficial effects. RT is increasingly establishing itself as an effective measure to improve overall metabolic health and reduce metabolic risk factors in diabetic patients. Barbara Strasser and Dominik Pesta Copyright © 2013 Barbara Strasser and Dominik Pesta. All rights reserved. Baseline Obesity Status Modifies Effectiveness of Adapted Diabetes Prevention Program Lifestyle Interventions for Weight Management in Primary Care Wed, 04 Dec 2013 14:40:16 +0000 Kristen M. J. Azar, Lan Xiao, and Jun Ma Copyright © 2013 Kristen M. J. Azar et al. All rights reserved. Effects of Water Extracts of Graptopetalum paraguayense on Blood Pressure, Fasting Glucose, and Lipid Profiles of Subjects with Metabolic Syndrome Mon, 25 Nov 2013 10:49:35 +0000 This study was aimed to investigate the effects of water extracts of Graptopetalum paraguayense (WGP, 4 g/d) on blood pressure, blood glucose level, and lipid profiles in subjects with metabolic syndrome (MS). Participants with MS () were randomly assigned to the placebo () and WGP groups (), and the intervention was administered for 12 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), lipid profiles (total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein (HDL-C)), and antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) were measured. Forty-two subjects completed the study (placebo, ; WGP, ). FG, SBP, and LDL-C levels were significantly lower and HDL-C level and antioxidant enzymes activities (CAT and SOD) were significantly higher after WGP supplementation. Blood pressure, FG, and lipid profiles were significantly correlated with antioxidant enzymes activities after supplementation (). The present study demonstrated a significant reduction in blood pressure, blood glucose, and lipid profiles and an increase in antioxidant enzymes activities in subjects with MS after WGP supplementation. Taken together, the antioxidative capacity of WGP might exert a beneficial effect on MS. This trial is registered with NCT01463748. Chi-Hua Yen, Shu-Ju Chen, Jen-Tzu Liu, Yu-Fen Tseng, and Ping-Ting Lin Copyright © 2013 Chi-Hua Yen et al. All rights reserved. IRS1, TCF7L2, ADRB1, PPARG, and HHEX Polymorphisms Associated with Atherogenic Risk in Mexican Population Mon, 25 Nov 2013 08:48:51 +0000 Objective. We aimed to explore the association between polymorphisms of IRS1 (rs1801278), TCF7L2 (rs7903146 and rs12255372), ADRB1 (rs1801253), PPARG (rs1801282), and HHEX (rs5015480) genes with atherogenic risk (AI = Total cholesterol/HDL) in MetS, T2D, and healthy populations from the Mexican Social Security Institute. Methodology and Results. Four hundred thirty-five MetS, 517 T2D, and 547 healthy individuals were selected. The association between the SNPs and the atherogenic index was evaluated by multiple linear regression and multinomial logistic regression models. The ADRB1 gene showed a statistically significant association with high-risk atherogenic index, (IC 95% 1.64–5.24; ) for the Arg/Gly variant, under the dominant model an (IC 95% 1.67–5.25; ), and under the Log additive model an (IC 95% 1.54–4.15; ). Conclusions. The Arg389Gly polymorphism of the ADRB1 gene may be a worthy biological marker to predict the risk of developing cardiovascular diseases given a high-risk atherogenic index. B. I. Estrada-Velasco, M. Cruz, V. Madrid-Marina, G. A. Martínez-Nava, J. Gomez-Zamudio, and A. I. Burguete-García Copyright © 2013 B. I. Estrada-Velasco et al. All rights reserved. Tyrosine Kinase Inhibitors Induced Thyroid Dysfunction: A Review of Its Incidence, Pathophysiology, Clinical Relevance, and Treatment Sun, 27 Oct 2013 17:42:20 +0000 Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multitargeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. Since their introduction as adjunct treatment for renal cell carcinoma and gastrointestinal stromal tumors (GIST), a number of reports have demonstrated that TKI can induce thyroid dysfunction which was especially more common with sunitinib maleate. Many mechanisms with respect to this adverse effect of tyrosine kinase inhibitors have been proposed including their induction of thyroiditis, capillary regression in the thyroid gland, antithyroid peroxidase antibody production, and their ability to decrease iodine uptake by the thyroid gland. Of interest is the observation that TKI-induced thyroid dysfunction may actually be protective as it was shown to improve overall survival, and it was suggested that it may have a prognostic value. Followup on thyroid function tests while patients are maintained on tyrosine kinase inhibitor is strongly recommended. When thyroid dysfunction occurs, appropriate treatment should be individualized depending on patients symptoms and thyroid stimulating hormone level. Hala Ahmadieh and Ibrahim Salti Copyright © 2013 Hala Ahmadieh and Ibrahim Salti. All rights reserved. The Incidence of Hypogonadotropic Hypogonadism in Type 2 Diabetic Men in Polish Population Thu, 10 Oct 2013 09:56:29 +0000 The aim of this study was to investigate the incidence of hypogonadotropic hypogonadism (HH) in type 2 diabetic men (T2DM) in population of Polish men and examine the possible influence of estradiol levels and glycemic control. We evaluated TT, cfT, estradiol, and glycemic control (HbA1c) in 184 diabetic men and in 149 nondiabetic control group. The mean HbA1c was 8.6 ± 0.2% and 6.1 ± 0.3% and cfT concentration was 0.315 ± 0.08 nmol/L and 0.382 ± 0.07 nmol/L, respectively. T2DM had higher E2 concentration than nonobese control men (29.4 ± 3.7 pg/mL versus 24.5 ± 2.9 pg/mL). Forty-six percent of T2DM were hypogonadal and 93% had HH. We observed inverse relationship between BMI and cfT (, ) and positive between BMI and E2 (, ). E2 concentration was higher in T2DM with HH versus T2DM with normal TT/cfT concentration (34.5 ± 5.2 versus 27.4 ± 3.4 pg/mL). We observed negative correlation between HbA1c and cfT (, ) but positive between HbA1c and E2 levels (, ). The prevalence of obesity, hypertension, and CVD was higher in men with hypogonadism. High incidence of hypogonadotropic hypogonadism in type 2 diabetic men in Polish population is associated with poor glycemic control and can be secondary to an increase in estradiol concentrations. Michał Rabijewski, Lucyna Papierska, Wojciech Zgliczyński, and Paweł Piątkiewicz Copyright © 2013 Michał Rabijewski et al. All rights reserved. Potential Utility of Sodium Selenate as an Adjunct to Metformin in Treating Type II Diabetes Mellitus in Rats: A Perspective on Protein Tyrosine Phosphatase Wed, 11 Sep 2013 13:57:25 +0000 Metformin is widely regarded as the standard first-line antidiabetic agent, in terms of efficacy and safety profiles. However, in most patients with type II diabetes mellitus (T2DM), it was found that metformin alone is not enough to adequately control hyperglycemia. Thus, we designed this study with the aim to investigate the effect of sodium selenate, a protein tyrosine phosphatase (PTP) inhibitor, individually and as an adjunct to metformin, on a rat model that simulates the metabolic characteristics of human T2DM. T2DM model was achieved by feeding the rats with high-fat, high-fructose diet (HFFD) for 8 weeks followed by a low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.). Changes in serum glucose, insulin, adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR) index, and the lipid profile were assessed. In addition, the level of reduced glutathione (GSH) and the activity of PTP were determined in the liver. Results showed that the addition of sodium selenate to metformin was able to restore hepatic GSH back to normal levels. Also, this combination therapy corrected the altered serum total cholesterol (TC), triglycerides (TG), and adiponectin levels. In conclusion, additive therapeutic effect was recorded when sodium selenate was used as an adjunct to metformin. Rania M. Salama, Mona F. Schaalan, Alaaeldin A. Elkoussi, and Amani E. Khalifa Copyright © 2013 Rania M. Salama et al. All rights reserved. Time Course of Improvement of Metabolic Parameters after a 12 Week Physical Exercise Programme in Patients with Type 2 Diabetes: The Influence of Gender in a Nigerian Population Thu, 29 Aug 2013 15:42:06 +0000 Gender is a major determinant of the outcomes of many health interventions. This study documents the order of significant improvements in metabolic parameters of patients with type 2 diabetes mellitus (T2DM) having metabolic syndrome within 12 weeks of physical exercise programmes. Twenty-nine patients, mean age 49.6 ± 3.7 years, presenting with high fasting plasma glucose, high triglycerides, hypertension, and high waist circumference undertook a thrice weekly aerobic and endurance exercise programme in addition to their drugs and diet. Variables were assessed at baseline and end of every two weeks for twelve weeks. Compared with baseline, significant improvement () in the metabolic parameters occurred in this order for the male participants: fasting glucose (2nd week), triglycerides and waist circumference (4th week), and systolic blood pressure (12th week). For the female participants, it was fasting glucose (4th week), triglycerides (6th week), and waist circumference (10th week). Regardless of the gender, fasting glucose was the first to improve significantly, followed by triglycerides. Hypertension did not improve significantly at all in the female participants as they may require more than twelve weeks of therapeutic exercise for any significant improvement in hypertension. A. F. Adeniyi, A. E. Uloko, O. O. Ogwumike, A. O. Sanya, and A. A. Fasanmade Copyright © 2013 A. F. Adeniyi et al. All rights reserved. Modulation of Pineal Melatonin Synthesis by Glutamate Involves Paracrine Interactions between Pinealocytes and Astrocytes through NF-B Activation Mon, 05 Aug 2013 08:54:42 +0000 The glutamatergic modulation of melatonin synthesis is well known, along with the importance of astrocytes in mediating glutamatergic signaling in the central nervous system. Pinealocytes and astrocytes are the main cell types in the pineal gland. The objective of this work was to investigate the interactions between astrocytes and pinealocytes as a part of the glutamate inhibitory effect on melatonin synthesis. Rat pinealocytes isolated or in coculture with astrocytes were incubated with glutamate in the presence of norepinephrine, and the melatonin content, was quantified. The expression of glutamate receptors, the intracellular calcium content and the NF-κB activation were analyzed in astrocytes and pinealocytes. TNF-α's possible mediation of the effect of glutamate was also investigated. The results showed that glutamate's inhibitory effect on melatonin synthesis involves interactions between astrocytes and pinealocytes, possibly through the release of TNF-α. Moreover, the activation of the astrocytic NF-κB seems to be a necessary step. In astrocytes and pinealocytes, AMPA, NMDA, and group I metabotropic glutamate receptors were observed, as well as the intracellular calcium elevation. In conclusion, there is evidence that the modulation of melatonin synthesis by glutamate involves paracrine interactions between pinealocytes and astrocytes through the activation of the astrocytic NF-κB transcription factor and possibly by subsequent TNF-α release. Darine Villela, Victoria Fairbanks Atherino, Larissa de Sá Lima, Anderson Augusto Moutinho, Fernanda Gaspar do Amaral, Rafael Peres, Thais Martins de Lima, Andréa da Silva Torrão, José Cipolla-Neto, Cristóforo Scavone, and Solange Castro Afeche Copyright © 2013 Darine Villela et al. All rights reserved. Chronic Exposure to Cadmium Disrupts the Adrenal Gland Activity of the Newt Triturus carnifex (Amphibia, Urodela) Mon, 22 Jul 2013 13:20:28 +0000 We intended to verify the safety of the freshwater values established for cadmium by the European Community and the Italian Ministry of Health in drinking water (5 μg/L) and sewage waters (20 μg/L). Therefore, we chronically exposed the newt Triturus carnifex to 5 μg/L and 20 μg/L doses of cadmium, respectively, during 3 and 9 months and verified the effects on the adrenal gland. We evaluated the serum concentrations of adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both doses of cadmium decreased ACTH and corticosterone serum levels and increased aldosterone and epinephrine serum levels. During the 9-month exposure, the 5 μg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels; the 20 μg/L dose decreased norepinephrine and epinephrine serum levels, without affecting the other hormones. It was concluded that (1) chronic exposure to the safety values established for cadmium disrupted the adrenal gland activity and (2) the effects of cadmium were related both to the length of exposure and the dose administered. Moreover, our results suggest probable risks to human health, due to the use of water contaminated by cadmium. Flaminia Gay, Vincenza Laforgia, Ivana Caputo, Carla Esposito, Marilena Lepretti, and Anna Capaldo Copyright © 2013 Flaminia Gay et al. All rights reserved. The Role of PTPN22 C1858T Gene Polymorphism in Diabetes Mellitus Type 1: First Evaluation in Greek Children and Adolescents Mon, 15 Jul 2013 10:48:55 +0000 Type 1 diabetes mellitus (T1DM) is an autoimmune multifactorial disease. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. PTPN22 C1858T polymorphism was associated with T1DM in populations of Caucasian origin. The aim of this study was the investigation for the first time of the association of PTPN22 C1858T polymorphism with T1DM in Greek population. We studied 130 children and adolescents with T1DM and 135 healthy individuals of Greek origin. The polymorphism was genotyped using polymerase chain reaction with restriction fragment length polymorphism. C1858T and T1858T genotypes as well as 1858T allele were found more frequently in patients (10.8% and 5.8%, resp.) than in healthy individuals (5.9% and 3.0%, resp.) but at non statistically significant level. There was no statistically significant association found with gender, age at diagnosis, severity of onset, history of Hashimoto thyroiditis or family history of T1DM. Increased frequency of 1858T allele in patients than in controls, implying a probable association, agrees with results of similar studies on other populations. The inability to find a statistically significant difference is probably due to the decreased frequency of minor allele in Greek population, indicating the need for a larger sample. Styliani Giza, Antonios Goulas, Emmanouela Gbandi, Smaragda Effraimidou, Efimia Papadopoulou-Alataki, Maria Eboriadou, and Assimina Galli-Tsinopoulou Copyright © 2013 Styliani Giza et al. All rights reserved. Prevalence of Overweight and Obesity in Urban Elementary School Children in Northeastern Romania: Its Relationship with Socioeconomic Status and Associated Dietary and Lifestyle Factors Sun, 14 Jul 2013 07:53:44 +0000 The purpose of this paper is to estimate the prevalence of obesity and to identify its potential determinants to optimize the methods of prevention to combat further increases in childhood overweight. The study was carried out on 3444 school children of 6–10 years of age attending 30 schools in northeast Romania. Schools were classified by geographical location and socioeconomic status (SES). Overweight and obesity status were determined using IOTF BMI cut-off points. Prevalence of overweight (including obesity) was found to be 24.6% among boys and 22.6% among girls, whereas the prevalence of obesity was 7.8% in boys and 6.3% in girls. High SES (OR: 1.46; 95% CI: 1.10–1.93) and eating French fries and chips (OR: 1.81; 95% CI: 1.24–2.67) were associated with increased risk of overweight. In high- and medium-SES children, overweight was positively associated with the consumption of French fries and chips (2.93, 95% CI: 1.54–5.60 and 1.82, 95% CI: 1.04–3.21). In low-SES children, overweight was associated with low fruit consumption (0.21, 95% CI: 0.05–1.00) and sedentary behavior (3.37, 95% CI: 1.13–10.05). Therefore, the social and environmental determinants should be considered when constructing and implementing preventive measures regarding overweight and obesity. Veronica Mocanu Copyright © 2013 Veronica Mocanu. All rights reserved. Leptin Modulates Norepinephrine-Mediated Melatonin Synthesis in Cultured Rat Pineal Gland Mon, 01 Jul 2013 15:46:07 +0000 Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1 nM) associated with NE (1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression of Icer mRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception. Rodrigo Antonio Peliciari-Garcia, Jéssica Andrade-Silva, José Cipolla-Neto, and Carla Roberta de Oliveira Carvalho Copyright © 2013 Rodrigo Antonio Peliciari-Garcia et al. All rights reserved. Lipoprotein(a) Serum Levels in Diabetic Patients with Retinopathy Wed, 05 Jun 2013 10:02:31 +0000 Background. Atherogenic lipoproteins, such as total cholesterol, LDL cholesterol, oxidized low density lipoprotein, and triglycerides, are associated with progression of retinopathy. Aim. To evaluate the relationship between lipoprotein(a) and retinopathy in patients with type 2 diabetes mellitus. Materials and Methods. We enrolled 145 diabetic consecutive patients (82 females, 63 males; mean age years, mean duration of diabetes years). Presence and severity of retinopathy were evaluated. Serum lipid profile, including Lp(a) level, was assessed. Results. High Lp(a) levels have been observed in 54 (78.3%) subjects and normal levels in 13 (18.85%) subjects as regards diabetic patients with retinopathy. Lp(a) levels were high in 15 subjects (21.75%) and normal in 63 subjects (91.35%) as regards patients without retinopathy. Conclusions. Lp(a) levels are increased in a significant percentage of patients with retinopathy compared to diabetic patients without retinopathy. The impact of Lp(a) levels on diabetic retinopathy needs to be further investigated. Giulia Malaguarnera, Caterina Gagliano, Claudio Bucolo, Marco Vacante, Salvatore Salomone, Michele Malaguarnera, Daniela Giovanna Leonardi, Massimo Motta, Filippo Drago, and Teresio Avitabile Copyright © 2013 Giulia Malaguarnera et al. All rights reserved. In Vivo Determination of Vitamin D Function Using Transgenic Mice Carrying a Human Osteocalcin Luciferase Reporter Gene Wed, 27 Mar 2013 15:44:28 +0000 Vitamin D is an essential factor for ossification, and its deficiency causes rickets. Osteocalcin, which is a noncollagenous protein found in bone matrix and involved in mineralization and calcium ion homeostasis, is one of the major bone morphogenetic markers and is used in the evaluation of osteoblast maturation and osteogenic activation. We established transgenic mouse line expressing luciferase under the control of a 10-kb osteocalcin enhancer/promoter sequence. Using these transgenic mice, we evaluated the active forms of vitamins D2 and D3 for their bone morphogenetic function by in vivo bioluminescence. As the result, strong activity for ossification was observed with 1α,25-hydroxyvitamin D3. Our mouse system can offer a feasible detection method for assessment of osteogenic activity in the development of functional foods and medicines by noninvasive screening. Tomoko Nakanishi, Rumiko Saito, Makoto Taniguchi, Haruka Oda, Atsumi Soma, Mayu Yasunaga, Mariko Yamane, and Kenzo Sato Copyright © 2013 Tomoko Nakanishi et al. All rights reserved. Vitamin D and Bone Disease Thu, 27 Dec 2012 09:20:15 +0000 Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a “good bone health” guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action. S. Christodoulou, T. Goula, A. Ververidis, and G. Drosos Copyright © 2013 S. Christodoulou et al. All rights reserved. Altered Polarization, Morphology, and Impaired Innate Immunity Germane to Resident Peritoneal Macrophages in Mice with Long-Term Type 2 Diabetes Wed, 03 Oct 2012 10:34:02 +0000 Type 2 diabetes (T2D) is associated with perturbed innate immunity. Macrophages, bridging innate immunity and metabolic disturbances, play important roles in controlling immune homeostasis. However, the effect of long-term diabetic milieu (DM) on the functions and phenotypes of macrophages is still not clear. In this study, we used resident peritoneal macrophages (RPMs) from 5-month-old db/db mice to investigate the changes of macrophages. It was found that RPMs in db/db mice significantly reduced phagocytosis and adhesion capacity. After standardization with body weight, the number of F4/80+ RPMs markedly reduced in db/db mice, and, furthermore, the macrophages skewed to M2-polarizated macrophages. The results of morphology found that the RPMs shape of db/db mice was nearly round, but the RPMs shape of control mice was spindle-shaped and irregular. In this study, we found the cell numbers, morphology, and innate immunity functions of RPMs in 5-month-old type 2 diabetic mice (db/db mice) obtained by abdominal cavity lavage were significantly altered. Importantly, we also found the remarkably increased M2-RPMs in diabetic mice for the first time. Hui-Fang Liu, Hui-Jie Zhang, Qi-Xian Hu, Xiao-Yan Liu, Zhi-Quan Wang, Jia-Yan Fan, Ming Zhan, and Feng-Ling Chen Copyright © 2012 Hui-Fang Liu et al. All rights reserved. Effects of Norepinephrine and Acetylcholine on the Development of Cultured Leydig Cells in Mice Tue, 02 Oct 2012 13:35:49 +0000 Few data have suggested how norepinephrine (NE) and acetylcholine (Ach) regulate the development of Leydig cells in mice at prepuberty, except for data indicating endocrine effects. The present study aims to elucidate the roles of NE and Ach on the differentiation and proliferation of Leydig cells. Firstly, the expression of adrenergic receptors and muscarinic acetylcholine receptors in Leydig cells was investigated. It was found that adrenergic receptors (β1AR, β2AR, and α1D) and muscarinic acetylcholine receptors (M1 and M3) mRNA are expressed in adult Leydig cells. Then, the effects of NE and Ach on the differentiation and proliferation of Leydig cells were analyzed. The results showed that NE and Ach at 10 μM significantly increased the number of 3β-hydroxysteroid-dehydrogenase- (3β-HSD-) positive Leydig cells and improved the expression of proliferating cell nuclear antigen (PCNA) in Leydig cells on postnatal day (PD) 15 (๐‘ƒ<0.05). NE and Ach at 10 μM had no impact on the expression of PCNA mRNA (๐‘ƒ>0.05), but reduced the expression of 3β-HSD mRNA in adult Leydig cells and a murine Leydig tumor cell line (MLTC-1) (๐‘ƒ<0.05). Therefore, a conclusion may be reached that NE and Ach participated in stimulating the development of Leydig cells in mice from prepuberty to adult stage. Shuying Huo, Xiuhui Zhong, Xianjun Wu, and Yurong Li Copyright © 2012 Shuying Huo et al. All rights reserved. Psychological Stress Alters Ultrastructure and Energy Metabolism of Masticatory Muscle in Rats Sun, 31 Oct 2010 14:18:32 +0000 To investigate the effects of psychological stress on the masticatory muscles of rats, a communication box was applied to induce the psychological stress (PS) in rats. The successful establishment of psychological stimulation was confirmed by elevated serum levels of adrenocorticotropic hormone (ACTH) and changed behaviors in the elevated plusmaze apparatus. The energy metabolism of the bilateral masseter muscles was tested via chemocolorimetric analysis, whereas muscle ultrastructure was assessed by electron microscopy. In comparison to the control group, the PS group showed evidence of swollen mitochondria with cristae loss and reduced matrix density in the masticatory muscles after three weeks of stimulation; after five weeks of stimulation, severe vacuolar changes to the mitochondria were observed. Increased vascular permeability of the masticatory muscle capillaries was found in the five-week PS rats. In addition, there was decreased activity of -ATPase and -ATPase and a simultaneous increase in the activity of lactate dehydrogenase and lactic acid in the masticatory muscles of PS rats. Together, these results indicate that psychological stress induces alterations in the ultrastructure and energy metabolism of masticatory muscles in rats. Yong-Jin Chen, Fei Huang, Min Zhang, and Hai-Yan Shang Copyright ยฉ 2010 Yong-Jin Chen et al. All rights reserved. Endocrine Disruptors and Leydig Cell Function Wed, 25 Aug 2010 08:01:59 +0000 During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs) on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed. K. Svechnikov, G. Izzo, L. Landreh, J. Weisser, and O. Söder Copyright © 2010 K. Svechnikov et al. All rights reserved. FSHR Single Nucleotide Polymorphism Frequencies in Proven Fathers and Infertile Men in Southeast Turkey Thu, 29 Apr 2010 07:19:10 +0000 The influence of FSH receptor (FSHR) variants on male infertility is not completely understood. The present investigation is the first screening study for SNP at nucleotide position −29 in the core promoter region and codon 680 in exon 10 of the FSHR and the effect of the serum levels of FSH on male infertility in Southeast Turkey. The SNPs in codon 680 and at position −29 of the FSHR gene were analyzed by PCR-RFLP technique in 240 men with proven fathers, and 270 infertile men (150 nonobstructive azoospermic and 120 severe oligozoospermic). The separate analysis for SNP at nucleotide position −29 did not show any difference in genotypic frequencies and serum FSH levels. The genotype distribution of SNP at position 680 was different but does not influence serum FSH levels. Together the two SNPs form four discrete haplotypes (A-Thr-Asn, G-Thr-Asn, A-Ala-Ser, and G-Ala-Ser) occurring in 10 combinations. A statistically significant difference in the allelic distribution of G-Asn/G-Ser and G-Ser/G-Ser genotype between proven fathers and infertile men but there were not any statistically significant difference in the overall frequency of the four FSHR haplotypes. We conclude that the FSHR haplotype does not associate with different serum FSH levels but it is differently distributed in proven fathers and infertile men. Mahmut Balkan, Abdullah Gedik, Hasan Akkoc, Ozlem Izci Ay, M. Emin Erdal, Hilmi Isi, and Turgay Budak Copyright © 2010 Mahmut Balkan et al. All rights reserved. Testosterone Depletion by Castration May Protect Mice from Heat-Induced Multiple Organ Damage and Lethality Mon, 12 Apr 2010 10:11:22 +0000 When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4โˆ˜Cยฑ0.3โˆ˜C, respectively. Castration 2 weeks before the start of heat stress decreased the plasma levels of testosterone almost to zero, protected the mice from heat-induced death (fraction survival, 13/15) and reduced the hypothermia (core temperature, 37.3โˆ˜C). The beneficial effects of castration in ameliorating lethality and hypothermia can be significantly reduced by testosterone replacement. Heat-induced apoptosis, as indicated by terminal deoxynucleotidyl- transferase- mediated๐›ผUDP-biotin nick end-labeling staining, were significantly prevented by castration. In addition, heat-induced neuronal damage, as indicated by cell shrinkage and pyknosis of nucleus, to the hypothalamus was also castration-prevented. Again, the beneficial effects of castration in reducing neuronal damage to the hypothalamus as well as apoptosis in multiple organs during heatstroke, were significantly reversed by testosterone replacement. The data indicate that testosterone depletion by castration may protect mice from heatstroke-induced multiple organ damage and lethality. Chian-Yuh Lin, Mao-Tsun Lin, Ruei-Tang Cheng, and Sheng-Hsien Chen Copyright © 2010 Chian-Yuh Lin et al. All rights reserved. In Vivo Bioassay of Recombinant Human Growth Hormone Synthesized in B. mori Pupae Thu, 18 Mar 2010 10:28:18 +0000 The human growth hormone (hGH) has been expressed in prokaryotic expression system with low bioactivity previously. Then the effective B. mori baculovirus system was employed to express hGH identical to mature hGH successfully in larvae, but the expression level was still limited. In this work, the hGH was expressed in B. mori pupae by baculovirus system. Quantification of recombinant hGH protein (BmrhGH) showed that the expression of BmrhGH reached the level of approximately 890 ๐œ‡g/mL pupae supernatant solution, which was five times more than the level using larvae. Furthermore, Animals were gavaged with BmrhGH at the dose of 4.5 mg/, and the body weight gain (BWG) of treated group had a significant difference (๐‘ƒ<.01) compared with the control group. The other two parameters of liver weight and epiphyseal width were also found to be different between the two groups (๐‘ƒ<.05). The results suggested that BmrhGH might be used as a protein drug by oral administration. Hanglian Lan, Zuoming Nie, Yue Liu, Zhengbing Lv, Yingshuo Liu, Yanping Quan, Jianqing Chen, Qingliang Zhen, Qin Chen, Dan Wang, Qing Sheng, Wei Yu, Jian Chen, Xiangfu Wu, and Yaozhou Zhang Copyright © 2010 Hanglian Lan et al. All rights reserved. The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System Wed, 02 Aug 2006 00:00:00 +0000 Background. The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results. A panel of mouse models including mice lacking angiotensinogen, Agt (Agt-KO), mice expressing Agt solely in adipose tissue (aP2-Agt/Agt-KO), and mice overexpressing Agt in adipose tissue (aP2-Agt) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. aP2-Agt mice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2-Agt mice. Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity. Suyeon Kim, Morvarid Soltani-Bejnood, Annie Quignard-Boulange, Florence Massiera, Michele Teboul, Gerard Ailhaud, Jung Han Kim, Naima Moustaid-Moussa, and Brynn H. Voy Copyright © 2006 Suyeon Kim et al. All rights reserved.