http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2013 , Hindawi Publishing Corporation . All rights reserved. Tue, 18 Jun 2013 14:40:17 +0000 http://www.hindawi.com/isrn/endocrinology/2013/427818/ The hormonally active form of vitamin D3, 1,25(OH)2D3 (calcitriol), exerts actions through VDR receptor, which acts as a transcriptional factor. Calcitriol is an immunomodulator that affects various immune cells, and several studies link it to many autoimmune diseases. BsmI polymorphism affects the level of VDR gene transcription, transcript stability, and posttranscriptional modifications. It seems to be related to the systemic lupus erythematosus (SLE). Our study examined the characteristics of VDR gene BsmI polymorphism in Polish SLE patients and their relationship with clinical manifestations of the disease. We genotyped 62 patients with SLE and 100 healthy controls using the real-time PCR. There were no differences observed in the frequency of BsmI genotypes in SLE patients and in the control group. There was no significant correlation between BsmI genotypes and clinical symptoms of SLE, but the AA genotype correlates with higher levels of antinuclear antibodies (ANA) in this group (; ). A larger study examining BsmI and other VDR gene polymorphisms is needed. It may allow explaining differences in the clinical picture of the disease and choosing a personalized therapy. Beata Kaleta, Jarosław Bogaczewicz, Ewa Robak, Anna Sysa-Jędrzejowska, Małgorzata Wrzosek, Weronika Szubierajska, Piotr Mróz, Jacek Łukaszkiewicz, and Anna Woźniacka Copyright © 2013 Beata Kaleta et al. All rights reserved. Tue, 11 Jun 2013 15:11:37 +0000 http://www.hindawi.com/isrn/endocrinology/2013/321063/ Background. Cushing’s syndrome (CS) is a relatively unusual condition that resembles many of the phenotypic features of obesity. Our aim was to evaluate the frequency of CS in obese patients. Materials and Methods. This study included 354 consecutive patients (87.9% female, age years) who presented with simple obesity. All the patients were evaluated for the clinical signs of CS. Lipid parameters, fasting glucose (FPG) and insulin, 75 gr oral glucose tolerance test, basal cortisol and ACTH were measured. 1 mg overnight DST was performed. Results. The mean weight of the patients was  kg and BMI  kg/m2. 34.5% of the patients were hypertensive. 36.2% of the patients had central obesity, 72% dorsocervical fat accumulation, 28.8% abdominal striae and 23.2% acne. 49.4% of the women had hirsutism. 46.5% had prediabetes and 12.0% had type 2 diabetes, 72.6% had dyslipidemia. The mean cortisol and ACTH levels were as follows:  μg/dL and  pg/mL. Seven patients failed to suppress plasma cortisol to less than 1.8 μg/dL. Biochemical confirmation tests were performed in these patients and 2 of them were diagnosed glucocorticoid-secreting adrenal adenoma. Conclusions. Routine screening for CS in obese patients is not required. Serap Baydur Sahin, Hacer Sezgin, Teslime Ayaz, Emine Uslu Gur, and Kadir Ilkkilic Copyright © 2013 Serap Baydur Sahin et al. All rights reserved. Tue, 11 Jun 2013 11:36:57 +0000 http://www.hindawi.com/isrn/endocrinology/2013/165397/ Understanding the molecular mechanisms underlying diabetic endothelial dysfunction is necessary in order to improve the cardiovascular health of diabetic patients. Previously, we described an in vivo, murine model of insulin resistance induced by feeding a high-fat diet (HFD) whereby the endothelium may be isolated by fluorescence-activated cell sorting (FACS) based on Tie2-GFP expression and cell-surface staining. Here, we apply this model to two new strains of mice, ScN/Tie2-GFP and ApoE(−/−)/Tie2-GFP, and describe their metabolic responses and endothelial isolation. ScN/Tie2-GFP mice, which lack a functional toll-like receptor 4 (TLR4), display lower fasting glucose and insulin levels and improved glucose tolerance compared to Tie2-GFP mice, suggesting that TLR4 deficiency decreases susceptibility to the development of insulin resistance. ApoE(−/−)/Tie2-GFP mice display elevated glucose and cholesterol levels versus Tie2-GFP mice. Endothelial isolation by FACS achieves a pure population of endothelial cells that retain GFP fluorescence and endothelial functions. Transcriptional analysis of the aortic and muscle endothelium isolated from ApoE(−/−)/Tie2-GFP mice reveals a reduced endothelial response to HFD compared to Tie2-GFP mice, perhaps resulting from preexisting endothelial dysfunction in the hypercholesterolemic state. These mouse models and endothelial isolation techniques are valuable for assessing diabetic endothelial dysfunction and vascular responses in vivo. April L. Darrow, J. Gregory Maresh, and Ralph V. Shohet Copyright © 2013 April L. Darrow et al. All rights reserved. Wed, 05 Jun 2013 16:31:00 +0000 http://www.hindawi.com/isrn/endocrinology/2013/341632/ Background. Serum lipids including total cholesterol (TC), triglycerides (TG), and low density lipoprotein cholesterol (LDL-C) are increased in pregnancy. Serum proprotein convertase subtilisin kexin 9 (PCSK9) is a significant player in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of the liver, inhibiting clearance of LDL-C. Therefore, our study assessed serum PCSK9 concentrations at parturition (Maternal) compared to a nonpregnant (Control) cohort, as well as between mother and newborn (Maternal and Newborn). Methods. Blood was collected from women at parturition and from umbilical cords. Serum lipids and PCSK9 were measured and data were analysed for significance by Mann-Whitney test at and presented as median levels. Spearman's correlations were made at a 95% confidence interval. Results. Serum PCSK9 was significantly higher in Maternal versus Control cohorts (493.1 versus 289.7 ng/mL; , resp.), while the Newborn cohort was significantly lower than Maternal (278.2 versus 493.1 ng/mL; , resp.). PCSK9 was significantly correlated with TC and HDL-C in Maternal and with TC, LDL-C, and HDL-C in Newborn cohorts. Conclusions. Our study provides the first quantitative report on PCSK9 in pregnancy (at parturition) and in umbilical cord blood. Further research will determine how these changes may affect lipoprotein levels during this physiological state. Patricia Peticca, Angela Raymond, Andrée Gruslin, Marion Cousins, Ejibunmi Adetola, Hussein Abujrad, Janice Mayne, and Teik Chye Ooi Copyright © 2013 Patricia Peticca et al. All rights reserved. Tue, 28 May 2013 14:54:33 +0000 http://www.hindawi.com/isrn/endocrinology/2013/867938/ The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation. Mark R. Garbrecht and Fred S. Lamb Copyright © 2013 Mark R. Garbrecht and Fred S. Lamb. All rights reserved. Sat, 25 May 2013 14:02:59 +0000 http://www.hindawi.com/isrn/endocrinology/2013/673146/ Objectives. Assess the prevalence of thyroid nodules and predictors of malignant origin in patients with autoimmune thyroid diseases. Patients and Methods. Retrospective study including 275 patients, 198 with Graves' disease and 77 with Hashimoto’s thyroiditis. Clinical and demographical data, ultrasonographical nodule characteristics, total thyroid volume and histological characteristics were recorded. Results. Graves’ disease: the prevalence of thyroid nodules and thyroid carcinoma were 27.78% and 5.05%, respectively. Older age (OR = 1.054; 95% CI = 1.029–1.080) and larger thyroid volumes (OR = 1.013; 95% CI = 1.003–1.022) increased the chance of nodules. Younger age (OR = 1.073; 95% CI = 1.020–1.128) and larger thyroid volume (OR = 1.018; 95% CI = 1.005–1.030) predicted thyroid carcinoma. Hashimoto’s thyroiditis: the prevalence of thyroid nodules and carcinomas were 50.7% and 7.8%, respectively. Nodules were predicted by thyroid volume (OR = 1.030; 95% CI = 1.001–1.062). We found higher number of nodules in patients with thyroid carcinoma than in those with benign nodules (3 versus 2; ). Patients with Hashimoto’s thyroiditis presented nodules more frequently than patients with Graves’ disease (50.65% versus 27.28%; ), while the prevalence of carcinoma was similar (). Conclusions. Larger goiter was associated with carcinoma in Graves’ disease and Hashimoto’s thyroiditis. Younger patients presented higher risk of papillary thyroid carcinoma in Graves’ disease. The prevalence of carcinoma was similar in both conditions. Priscila Carneiro Moreira Lima, Arnaldo Moura Neto, Marcos Antonio Tambascia, and Denise Engelbrecht Zantut Wittmann Copyright © 2013 Priscila Carneiro Moreira Lima et al. All rights reserved. Thu, 09 May 2013 08:25:51 +0000 http://www.hindawi.com/isrn/endocrinology/2013/858690/ Objective. Diabetic nephropathy is the most commonly seen cause of chronic renal failure, and oxidative stress is important in etiology. In the present study, favorable effects (if any) of the treatment with a thiazolidinedione group drug, pioglitazone, on antioxidant enzyme levels in the renal tissue, renal histopathology, and inflammatory cytokine levels have been investigated. Method. Forty male Wistar rats were divided into 4 groups as the control, diabetic control, and 10 and 30 mg pioglitazone-administered diabetic groups. After 4 weeks, antioxidant enzyme levels in renal tissues and inflammatory markers were investigated. Results. Blood glucose levels did not differ between the diabetic control and drug-administered groups. In pioglitazone-administered rats, histopathological findings such as tubular dilation, necrotic tubular epithelium, glomerular focal necrosis, and vascular consolidation were observed at a lesser extent than the diabetic control group. Any difference was not detected between the diabetic groups with respect to the levels of malondialdehyde, superoxide dismutase, catalase, glutathione, nitric oxide, interleukin-6, and tumor necrosis factor-alpha. Conclusion. Pioglitazone regressed development of histopathological lesions such as glomerular focal necrosis, tubular epithelial necrosis, tubular dilation, and vascular wall consolidation. However, any favorable effect on antioxidant enzyme levels in renal tissues and inflammation markers was not detected. Munire Kuru Karabas, Mediha Ayhan, Engin Guney, Mukadder Serter, and Ibrahim Meteoglu Copyright © 2013 Munire Kuru Karabas et al. All rights reserved. Tue, 16 Apr 2013 10:51:36 +0000 http://www.hindawi.com/isrn/endocrinology/2013/934797/ The study focuses on polyherbal antidiabetic formulations of different plants used in the treatment of diabetes mixed in different concentrations. In the present study eleven medicinal plants with proven antidiabetic and related beneficial effects were selected for the preparation of five mixtures. The efficacy of prepared mixtures has been tested on streptozotocin- (STZ-) induced diabetic rats and compared with a commercially available drug glibenclamide. The mixtures at the dose levels of 400 mg/kg b.w. produced a significant decrease in blood glucose level by 69.6%, 70.97%, 64.45%, 71.82%, and 64.44% after 21 days of treatment. The elevated level of SGPT, SGOT, and ALP in the diabetic controlled group reflected the significant alteration of liver function by STZ induction and was found to be equipotent to glibenclamide in restoration of the elevated enzyme levels to normal. The elevated lipid levels (triglyceride and total cholesterol) were restored to near normal by these mixtures for all the estimated parameters. The results of the mixtures on treated group were found to restore the glycemic level to the near normal level thereby indicating antihyperglycemic activity of the formulated mixtures. Aparajeya Panda, Somanatha Jena, Pramod Kumar Sahu, Sanghamitra Nayak, and Payodhar Padhi Copyright © 2013 Aparajeya Panda et al. All rights reserved. Mon, 15 Apr 2013 17:50:46 +0000 http://www.hindawi.com/isrn/endocrinology/2013/385940/ Problem Statement. Thyroid disorders are prevalent in western Kenya, but the effects of disorders on thyroid hormones and hematological indices levels have not been documented. Study Population. Patients treated for thyroid disorders at the MTRH between January 2008 and December 2011. Objectives. To determine the thyroid hormones and hematological indices levels in thyroid disorders patients at the MTRH, western Kenya. Methodology. A retrospective study in which patient data and stored samples of patients, who presented with thyroid pathologies, underwent thyroidectomy, and histological examinations are done. Thyroid stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) blood levels, white blood cells (WBCs), red blood cells (RBCs), platelet counts, and hemoglobin (Hb) levels were analyzed. Results. Male : female ratio was 1 : 10.9 with female representing 368 (95%). The median age was 41 (IQR: 32–48) with a range of 14–89 years. HHormonal levels for immunological thyroid disease patients were higher (; 0.040) for TSH and (T3) for those aged 30–39 years, respectively. The WBCs, RBCs, HGB, and platelets in immunological thyroid disease were not statistically significant with values of 0.547, 0.205, 0.291, and 0.488 respectively. Conclusion. The presence of anaemia due to low RBCs in thyroid disease is not significantly associated with thyroid hormone with a value of 0.512. M. A. Iddah, B. N. Macharia, A. G. Ng’wena, A. Keter, and A. V. O. Ofulla Copyright © 2013 M. A. Iddah et al. All rights reserved. Sun, 31 Mar 2013 11:55:35 +0000 http://www.hindawi.com/isrn/endocrinology/2013/349604/ The advent of improved glucose control with insulin and oral medications has allowed for the diabetic population to live longer and healthier lives. Unfortunately diabetes remains a worldwide epidemic with multiple health implications. Specifically, its affects upon fracture healing have been well studied and shown to have negative effects on bone mineral density, biomechanical integrity, and fracture healing. Multiple animal models have been used for research purposes to gain further insight into the effects and potential treatments of this disease process. The diabetic BB Wistar rat is one model that replicates a close homology to human type-1 diabetes and has been used as a fracture model to study the effects of diabetes on bone integrity and healing. In particular, the effects of tight glucose control, ultrasound therapy, platelet-rich plasma (PRP), platelet-derived growth factor (PDGF), bone morphogenetic protein 2 (BMP-2), and allograft bone incorporation have been studied extensively. We present a review of the literature using the BB Wistar rat to elucidate the implications of diabetes on fracture healing. Amit Sood, Catie Cunningham, and Sheldon Lin Copyright © 2013 Amit Sood et al. All rights reserved. Thu, 14 Mar 2013 14:18:29 +0000 http://www.hindawi.com/isrn/endocrinology/2013/348705/ Data were pooled from four randomized clinical trials with vitamin D performed in Tromsø with weight reduction, insulin sensitivity, bone density, and depression scores as endpoints. Serum lipids, glycated hemoglobin (), and high sensitivity C-Reactive Protein, (HS-CRP) were measured at baseline and after 6–12 months of supplementation with vitamin D 20 000 IU–40 000 IU per week versus placebo. A total of 928 subjects who completed the interventions were included. At baseline the mean serum 25-hydroxyvitamin D (25(OH)D) level in those given vitamin D was 55.9 (20.9) nmol/L and the mean increase was 82.4 (40.1) nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight, but significant, increase in of 0.04%, an increase in HS-CRP of 0.07 mg/L in those with serum 25(OH)D < 50 nmol/L, and in those with low baseline HDL-C and serum 25(OH)D < 50 nmol/L a slight decrease serum HDL-C of 0.08 mmol/L (). No serious side-effects were seen. In conclusion, in subjects without vitamin D deficiency, there is no improvement in serum lipids, , or HS-CRP with high dose vitamin D supplementation. If anything, the effect is negative. Rolf Jorde, Moira Strand Hutchinson, Marie Kjærgaard, Monica Sneve, and Guri Grimnes Copyright © 2013 Rolf Jorde et al. All rights reserved. Mon, 11 Mar 2013 09:47:35 +0000 http://www.hindawi.com/isrn/endocrinology/2013/346987/ Type 1 diabetes is a metabolic disease caused by autoimmunity towards β-cells. Different strategies have been developed to restore β-cell function and to reestablish immune tolerance to prevent and cure the disease. Currently, there is no effective treatment strategy to restore endogenous insulin secretion in patients with type 1 diabetes. This study aims to restore insulin secretion in diabetic mice with experimental antigen-specific immunotherapy alone or in combination with rapamycin, a compound well known for its immunomodulatory effect. Nonobese diabetic (NOD) mice develop spontaneous type 1 diabetes after 12 weeks of age. Autologous tolerogenic dendritic cells—consisting in dendritic cells pulsed with islet apoptotic cells—were administered to diabetic NOD mice alone or in combination with rapamycin. The ability of this therapy to revert type 1 diabetes was determined by assessing the insulitis score and by measuring both blood glucose levels and C-peptide concentration. Our findings indicate that tolerogenic dendritic cells alone or in combination with rapamycin do not ameliorate diabetes in NOD mice. These results suggest that alternative strategies may be considered for the cure of type 1 diabetes. Irma Pujol-Autonell, Rosa M. Ampudia, Pau Monge, Anna M. Lucas, Jorge Carrascal, Joan Verdaguer, and Marta Vives-Pi Copyright © 2013 Irma Pujol-Autonell et al. All rights reserved. Wed, 27 Feb 2013 14:19:14 +0000 http://www.hindawi.com/isrn/endocrinology/2013/320176/ Background. The prevalence of metabolic syndrome (MetS) within individual cohorts varies with the definition used. The aim of this study was to compare the prevalence of MetS between IDF and revised NCEP ATP III criteria in an urban Sri Lankan population and to investigate the characteristics of discrepant cases. Methods. 2985 individuals, aged 35–65 years, were recruited to the study. Anthropometric and blood pressure measurements and laboratory investigations were carried out following standard protocols. Results. Age and sex-adjusted prevalences of MetS were 46.1% and 38.9% by revised NCEP and IDF definitions, respectively. IDF criteria failed to identify 21% of men and 7% of women identified by the revised NCEP criteria. The discrepant group had more adverse metabolic profiles despite having a lower waist circumference than those diagnosed by both criteria. Conclusion. MetS is common in this urban Sri Lankan cohort regardless of the definition used. The revised NCEP definition was more appropriate in identifying the metabolically abnormal but nonobese individuals, especially among the males predisposed to type 2 diabetes or cardiovascular disease. Further research is needed to determine the suitability of the currently accepted Asian-specific cut-offs for waist circumference in Sri Lankan adults. S. Chackrewarthy, D. Gunasekera, A. Pathmeswaren, C. N. Wijekoon, U. K. Ranawaka, N. Kato, F. Takeuchi, and A. R. Wickremasinghe Copyright © 2013 S. Chackrewarthy et al. All rights reserved. Sun, 17 Feb 2013 14:38:12 +0000 http://www.hindawi.com/isrn/endocrinology/2013/638028/ One experimental model of diabetes mellitus (DM) similar to type II DM, called n5-STZ, is obtained by a single injection (via i.p.) of streptozotocin (STZ) in the 5th day of life of newborn rats. The present investigation aimed to characterize alterations in excitability of rat peripheral neurons in n5-STZ model. n5-STZ DM was induced, and electrophysiological evaluation was done at 12th week of rat life. Rats developed glucose intolerance, sensory alteration, and hyperglycemia or near-normoglycemia ( and  mmol/L). In near-normoglycemia group the significant electrophysiological alteration observed was decreased in amplitude of 2nd wave (2nd component, conduction velocity: 48.8 m/s) of compound action potential (CAP) of sciatic nerve. For hyperglycemic rats, decreased excitability, amplitude, and conduction velocity of 2nd CAP component of sciatic nerve were found; a depolarization of resting potential (4-5 mV) and reduction in maximum ascendant and descendant inclinations of action potential were found in DRG neurons but no alteration on Na+ current (). Thus, n5-STZ rats develop alterations in excitability which were related to glycemic levels but were not likely attributable to changes on . Our data confirm that n5-STZ model is a useful model to study type II DM. Francisco Walber Ferreira-da-Silva, Kerly Shamyra da Silva-Alves, Matheus Lemos-dos-Santos, Keciany Alves de Oliveira, Humberto Cavalcante Joca, Otoni Cardoso do Vale, Andrelina Noronha Coelho-de-Souza, and José Henrique Leal-Cardoso Copyright © 2013 Francisco Walber Ferreira-da-Silva et al. All rights reserved. Wed, 13 Feb 2013 16:07:42 +0000 http://www.hindawi.com/isrn/endocrinology/2013/608313/ The escalating incidence of diabetic mellitus has given rise to the increasing problems of chronic diabetic ulcers that confront the practice of medicine. Peripheral vascular disease, neuropathy, and infection contribute to the multifactorial pathogenesis of diabetic ulcers. Approaches to the management of diabetic ulcers should start with an assessment and optimization of the patient’s general conditions, followed by considerations of the local and regional factors. This paper aims to address the management strategies for wound bed preparation in chronic diabetic foot ulcers and also emphasizes the importance of preventive measures and future directions. The “TIME” framework in wound bed preparation encompasses tissue management, inflammation and infection control, moisture balance, and epithelial (edge) advancement. Tissue management aims to remove the necrotic tissue burden via various methods of debridement. Infection and inflammation control restores bacterial balance with the reduction of bacterial biofilms. Achieving a moist wound healing environment without excessive wound moisture or dryness will result in moisture balance. Epithelial advancement is promoted via removing the physical and biochemical barriers for migration of epithelium from wound edges. These systematic and holistic approaches will potentiate the healing abilities of the chronic diabetic ulcers, including those that are recalcitrant. Arman Zaharil Mat Saad, Teng Lye Khoo, and Ahmad Sukari Halim Copyright © 2013 Arman Zaharil Mat Saad et al. All rights reserved. Thu, 07 Feb 2013 09:47:13 +0000 http://www.hindawi.com/isrn/endocrinology/2013/463939/ Objectives. The aim of the current study was to investigate the growth status of CH, generate specialized growth charts of CH infants, and compare them with their counterparts of regional normal infants. Methods. In this prospective cohort study, 760 (345 girls and 415 boys) neonates born in 2002–2009 diagnosed by neonatal CH screening program in Isfahan were followed up from the time of diagnosis. 552 healthy children were recruited as a control group. The empirical 3rd, 15th, 50th, 85th, and 97th percentiles for height, weight, and head circumference of both sexes were determined and compared with their counterpart values of the control group. The relative frequency of patients with impaired growth for each studied variable was determined. Also, specialized growth charts of CH patients were generated. Results. The percentiles of weight, height, and head circumference of studied patients are significantly different from regional healthy children (). The relative frequency of impaired head circumference was decreased to less than 3% at the 3rd year of age and for height it reached gradually 3% and 9% at the 5th year of age for boys and girls, respectively (); however for weight still it was statistically more than 3% in both sexes. Conclusion. CH patients had impaired growth development which was improved during follow up, but the catch-up time was earlier for head circumference and later for weight. Awat Feizi, Mahin Hashemipour, Silva Hovsepian, Zeynab Amirkhani, Roya Kelishadi, Maryam Yazdi, Kamal Heydari, Ali Sajadi, and Masoud Amini Copyright © 2013 Awat Feizi et al. All rights reserved. Sun, 03 Feb 2013 14:58:08 +0000 http://www.hindawi.com/isrn/endocrinology/2013/329606/ Insulin resistance is a common finding in chronic kidney disease (CKD) and is manifested by mild fasting hyperglycemia and abnormal glucose tolerance testing. Circulating levels of glucocorticoids are high. In muscle, changes in the insulin signaling pathway occur. An increase in the regulatory p85 subunit of Class I phosphatidylinositol 3-Kinase enzyme leads to decreased activation of the downstream effector protein kinase B (Akt). Mechanisms promoting muscle proteolysis and atrophy are unleashed. The link of Akt to the ubiquitin proteasome pathway, a major degradation pathway in muscle, is discussed. Another factor associated with insulin resistance in CKD is angiotensin II (Ang II) which appears to induce its intracellular effects through inflammatory cytokines or reactive oxygen species. Skeletal muscle ATP is depleted and the ability of AMP-activated protein kinase (AMPK) to replenish energy stores is blocked. How this can be reversed is discussed. Interleukin-6 (IL-6) levels are elevated in CKD and impair insulin signaling at the level of IRS-1. With exercise, IL-6 levels are reduced; glucose uptake and utilization are increased. For patients with CKD, exercise may improve insulin signaling and build up muscle. Treatment strategies for preventing muscle atrophy are discussed. James L. Bailey Copyright © 2013 James L. Bailey. All rights reserved. Wed, 30 Jan 2013 08:05:57 +0000 http://www.hindawi.com/isrn/endocrinology/2013/472432/ Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver pathologies and is associated with obesity and the metabolic syndrome, which represents a range of fatty liver diseases associated with an increased risk of type 2 diabetes. Molecular mechanisms underlying how to make transition from simple fatty liver to nonalcoholic steatohepatitis (NASH) are not well understood. However, accumulating evidence indicates that deregulation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway in hepatocytes is a common molecular event associated with metabolic dysfunctions including obesity, metabolic syndrome, and the NAFLD. A tumor suppressor PTEN negatively regulates the PI3K/AKT pathways through its lipid phosphatase activity. Molecular studies in the NAFLD support a key role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis, and fibrosis. We review recent studies on the features of the PTEN and the PI3K/AKT pathway and discuss the protein functions in the signaling pathways involved in the NAFLD. The molecular mechanisms contributing to the diseases are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies for a condition. Satoru Matsuda, Mayumi Kobayashi, and Yasuko Kitagishi Copyright © 2013 Satoru Matsuda et al. All rights reserved. Mon, 21 Jan 2013 10:25:08 +0000 http://www.hindawi.com/isrn/endocrinology/2013/723432/ The aim of this study was to clarify the relationship between the histological features of GH-producing adenomas surgically resected at the Toranomon Hospital and the clinical features of the patients. Histological examinations, including immunohistochemistry for anterior pituitary hormones and cytokeratin (CK), were performed on 242 consecutively excised GH-producing pituitary adenomas. Immunohistochemistry showed 45% of the adenomas to be monohormonal and 55% to be plurihormonal, producing GH-PRL (77%), GH-TSH (13%), and GH-PRL-TSH (10%). One-fourth of the monohormonal GH adenomas had a dot-like pattern of CK immunoreactivity in the majority of the tumor cells (>80%); they were significantly more common in female or younger patients and usually tended to be larger and more invasive than monohormonal GH adenomas with perinuclear CK. Interestingly, CK-immunonegative adenomas were found in only 5% of the patients; they also showed a tendency to be larger, suggesting that they are a distinct type of GH adenoma with clinically aggressive features. Serum hormone levels correlated well with tumor size only in GH-producing adenomas with a perinuclear pattern of CK immunoreactivity. Each histological subtype of adenoma, classified according to the pattern of CK immunoreactivity, was associated with distinct clinical characteristics. This information is useful for understanding the pathophysiology of acromegaly-causing GH-producing adenomas. Ryosuke Mori, Naoko Inoshita, Junko Takahashi-Fujigasaki, Tatsuhiro Joki, Hiroshi Nishioka, Toshiaki Abe, Takeshi Fujii, and Shozo Yamada Copyright © 2013 Ryosuke Mori et al. All rights reserved. Thu, 17 Jan 2013 15:15:57 +0000 http://www.hindawi.com/isrn/endocrinology/2013/181240/ Breast cancer is among the most common cancers worldwide. Diabetes is an important chronic health problem associated with insulin resistance, increased insulin level, changes in growth hormones and factors, and activation of mitogen-activating protein kinase (MAPK) pathways, leading to an increased breast cancer risk. This paper looked at the epidemiologic studies of the association between type 2 diabetes and risk of breast cancer and its effect on overall cancer-specific survival. The combined evidence overall supported a modest association between type 2 diabetes and the risk of breast cancer, which was found to be more prevalent among postmenopausal women. Effect of oral diabetics and insulin therapy on breast cancer risk was also evaluated. It was found that metformin and thiazolidinones tended to have a protective role. Metformin therapy trials for its use as an adjuvant for breast cancer treatment are still ongoing. Sulfonylurea and insulin therapy were found to be mildly associated with increased overall cancers. No evidence or studies evaluated the association of DPPIV inhibitors and GLP 1 agonists with breast cancer risk because of their recent introduction into the management of diabetes. Hala Ahmadieh and Sami T. Azar Copyright © 2013 Hala Ahmadieh and Sami T. Azar. All rights reserved. Tue, 15 Jan 2013 16:24:32 +0000 http://www.hindawi.com/isrn/endocrinology/2013/148497/ Background. Hypercortisolism and type 2 diabetes (T2D) share clinical characteristics. We examined pioglitazone's effects on the GH-IGF-I and HPA axes in men with varying glucose intolerance. Methods. 10 men with T2D and 10 with IGT received pioglitazone 30–45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 μg ACTH-stimulation test were performed before and after. Glucose, insulin, IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT. Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups. IGF-I was initially lower in T2D subjects () and increased during treatment ( to SD; ); no change was seen in IGT ( SD before and during treatment). Fasting glycerol decreased in T2D (), indicating reduced lipolysis. Fasting cortisol decreased in T2D ( to  nmol/L; ) but increased in IGT ( to  nmol/L; ). Peak cortisol was lower in T2D during treatment ( to , versus to  nmol/L in IGT; ). Conclusions. Pioglitazone improved adipose tissue and liver insulin sensitivity in both groups. This may explain increased IGF-I in T2D. Pioglitazone affected cortisol levels in both groups but differently, suggesting different mechanisms for improving insulin sensitivity between T2D and IGT. Lisa Arnetz, Neda Rajamand Ekberg, Charlotte Höybye, Kerstin Brismar, and Michael Alvarsson Copyright © 2013 Lisa Arnetz et al. All rights reserved. Mon, 31 Dec 2012 12:33:04 +0000 http://www.hindawi.com/isrn/endocrinology/2012/675310/ Context. The literature concerning the health-related quality of life (HRQoL) of patients with surgically treated PA is controversial. Objective. To describe the long-term HRQoL of surgically treated patients in all PA classes. Design and subjects. The 15D, a generic HRQoL instrument producing a 15-dimensional profile and a single 15D index score (a difference ≥0.03 on a 0-1 scale is considered clinically important), was used to assess the HRQoL of a 13-year surgical cohort of PA patients in Northern Finland. Results and Conclusion. Nighty-eight eligible consecutive patients with surgically treated PA were studied at an average of 6.3 years after their latest pituitary operation. The average postoperative 15D profiles in patients with non-functioning PA and in acromegalics without GH-suppressive medical treatment were similar to those of the age-standardized general population. However, after this rather long followup, the mean 15D score and the number of statistically significant 15D dimension impairments, compared with those of their reference population, were 0.11 and 9/15, 0.10 and 3/15, and 0.08 and 7/15 for Cushing’s disease, acromegalics needing somatostatin analog, and prolactinoma patients, respectively. Hypopituitarism with replacement medication was not associated with impaired HRQoL. The somatostatin-analog-associated HRQoL finding warrants further clinical research. A. Raappana, T. Pirilä, T. Ebeling, P. Salmela, H. Sintonen, and J. Koivukangas Copyright © 2012 A. Raappana et al. All rights reserved. Thu, 27 Dec 2012 17:18:46 +0000 http://www.hindawi.com/isrn/endocrinology/2012/640956/ The pancreas is composed of two compartments that deliver digestive enzymes and endocrine hormones to control the blood sugar level. The endocrine pancreas consists of functional units organized into cell clusters called islets of Langerhans where insulin-producing cells are found in the core and surrounded by glucagon-, somatostatin-, pancreatic polypeptide-, and ghrelin-producing cells. Diabetes is a devastating disease provoked by the depletion or malfunction of insulin-producing beta-cells in the endocrine pancreas. The side effects of diabetes are multiple, including cardiovascular, neuropathological, and kidney diseases. The analyses of transgenic and knockout mice gave major insights into the molecular mechanisms controlling endocrine pancreas genesis. Moreover, the study of animal models of pancreas injury revealed that the pancreas has the propensity to undergo regeneration and opened new avenues to develop novel therapeutic approaches for the treatment of diabetes. Thus, beside self-replication of preexisting insulin-producing cells, several potential cell sources in the adult pancreas were suggested to contribute to beta-cell regeneration, including acinar, intraislet, and duct epithelia. However, regeneration in the adult endocrine pancreas is still under controversial debate. Ahmed Mansouri Copyright © 2012 Ahmed Mansouri. All rights reserved. Mon, 17 Dec 2012 16:30:49 +0000 http://www.hindawi.com/isrn/endocrinology/2012/126720/ Background. Chronic autoimmune thyroiditis (CAT) frequently alters thyroid vascularization, likely as a result of the autoimmune process. Objective. To evaluate the effects of low-level laser therapy (LLLT) on the thyroid vascularization of patients with hypothyroidism induced by CAT using color Doppler ultrasound parameters. Methods. In this randomized clinical trial, 43 patients who underwent levothyroxine replacement for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (L group, ) or 10 sessions of a placebo treatment (P group, ). Color Doppler ultrasounds were performed before and 30 days after interventions. To verify the vascularity of the thyroid parenchyma, power Doppler was performed. The systolic peak velocity (SPV) and resistance index (RI) in the superior (STA) and inferior thyroid arteries (ITAs) were measured by pulsed Doppler. Results. The frequency of normal vascularization of the thyroid lobes observed in the postintervention power Doppler examination was significantly higher in the L than in the P group (). The pulsed Doppler examination revealed an increase in the SPV of the ITA in the L group compared with the P group (). No significant differences in the SPV of the STA and in the RI were found between the groups. Conclusion. These results suggest that LLLT can ameliorate thyroid parenchyma vascularization and increase the SPV of the ITA of patients with hypothyroidism caused by CAT. Danilo Bianchini Höfling, Maria Cristina Chavantes, Adriana G. Juliano, Giovanni G. Cerri, Meyer Knobel, Elisabeth M. Yoshimura, and Maria Cristina Chammas Copyright © 2012 Danilo Bianchini Höfling et al. All rights reserved. Tue, 11 Dec 2012 14:14:15 +0000 http://www.hindawi.com/isrn/endocrinology/2012/630861/ Genetic susceptibility plays a key role in type 1 diabetes development. Because miR-541 gene was located within the associated chromosome loci and its target genes include the diabetes-associated gene neurogenin3, this study aimed to investigate whether miR-541 had type 1 diabetes-associated genetic variations. Type 1 diabetes children and healthy volunteers were recruited; direct sequencing was performed in initial 69 patients and 46 volunteers. We identified 1 reported SNP (rs12893725) and 3 novel genetic variations, for the candidate -404 G→T variation, restriction fragment length polymorphism (RFLP) was performed in total 247 diabetes children and 212 healthy volunteers, a different distribution trait of allele frequencies was found between the two groups, and further clinical analysis found no significant correlation between clinical parameter and genotypes among patients. In addition, by luciferase reporter assay, -404 was found to be within putative promoter region of pre-miR-541; although mutation of G→T has no effect on promoter activity, a significant secondary structure alteration may possibly influence its processing and transcription. In conclusion, we identified 3 novel genetic variations in putative promoter of miR-541 in type 1 diabetes patients; -404 G→T of miR-541 is a potential T1D-associated genetic variation. Bei Han, Xing Shi, Quan Peng, and Wentao Gao Copyright © 2012 Bei Han et al. All rights reserved. Sun, 09 Dec 2012 09:37:19 +0000 http://www.hindawi.com/isrn/endocrinology/2012/787201/ Cortisol production in adipose tissue is regulated by 11β-HSD1. Objective. To determine whether there are differences in gene expression, enzyme activity, and protein content of the 11β-HSD1 enzyme in VAT (visceral adipose tissue) and SAT (subcutaneous adipose tissue) from obese compared to nonobese adults. Methods. VAT and SAT samples were obtained from 32 obese subjects ( Kg/m2) who underwent bariatric surgery and 15 samples from controls submitted to elective surgery. Fasting serum glucose, insulin, and lipids were measured. The expression of 11β-HSD1 was determined by RT-PCR, the enzyme activity by thin-layer chromatography, and the protein content by Western blot. Results. Obese patients had higher cholesterol, insulin, and HOMA-IR compared to nonobese. There were no differences in VAT or SAT expression of 11β-HSD1 between obese and nonobese patients. However, we found lower 11β-HSD1 activity and protein content in VAT, in obese women versus nonobese women (). BMI and 11β-HSD1 enzyme activity and protein content in VAT correlated inversely in women. Conclusions. Regulation of 11β-HSD1 activity in VAT from obese subjects appears to be gender specific, suggesting the existence of a possible protective mechanism modulating this enzyme activity leading to a decrease in the production of cortisol in this tissue. A. Torres, G. Iñiguez, M. Ferrario, and V. Mericq Copyright © 2012 A. Torres et al. All rights reserved. Tue, 04 Dec 2012 08:52:17 +0000 http://www.hindawi.com/isrn/endocrinology/2012/168264/ Cardiac autonomic neuropathy (CAN) is a critical complication of type 2 diabetes mellitus (T2DM). Heart rate variability (HRV) is a noninvasive tool to assess cardiac autonomic function. We aimed to evaluate whether CAN is associated with increased risk of atherosclerosis in T2DM. A total of 57 diabetic and 54 nondiabetic subjects, free of coronary heart disease, were recruited. Carotid intima media thickness (CIMT), coronary calcium score (CAC), and brachial Flow Mediated Dilation (FMD) were measured. Heart rate variability and vagal components of autonomic function were determined. Significant reduction of normalized HF power and total power was observed in T2DM. CIMT and CAC scores were significantly higher while FMD was significantly lower in diabetics ( for all). Median HbA1c levels were significantly higher in diabetics. CIMT was inversely and independently associated with total power both in diabetics and controls ( for both groups). There was also an inverse association between total power and median HbA1c. Autonomic dysfunction, especially parasympathetic neuropathy, was present since early-stage T2DM. This was related to subclinical atherosclerosis. Early detection of cardiac autonomic neuropathy can help us detect the development of atherosclerosis earlier in T2DM to prevent unfavorable outcomes. Hossein Fakhrzadeh, Ahmad Yamini-Sharif, Farshad Sharifi, Yaser Tajalizadekhoob, Mojde Mirarefin, Maryam Mohammadzadeh, Saeed Sadeghian, Zohre Badamchizadeh, and Bagher Larijani Copyright © 2012 Hossein Fakhrzadeh et al. All rights reserved. Sun, 02 Dec 2012 08:51:54 +0000 http://www.hindawi.com/isrn/endocrinology/2012/318194/ While significant research has clearly identified sedentary behavior as a risk factor for type 2 diabetes and its subsequent complications, the concept that inactivity could be linked to the complications associated with type 1 diabetes (T1D) remains underappreciated. This paper summarizes the known effects of exercise on T1D at the tissue level and focuses on the pancreas, bone, the cardiovascular system, the kidneys, skeletal muscle, and nerves. When possible, the molecular mechanisms underlying the benefits of exercise for T1D are elucidated. The general benefits of increased activity on health and the barriers to increased exercise specific to people with T1D are discussed. Lisa Stehno-Bittel Copyright © 2012 Lisa Stehno-Bittel. All rights reserved. Thu, 29 Nov 2012 08:59:05 +0000 http://www.hindawi.com/isrn/endocrinology/2012/325092/ Thyroid disease is a common condition, and thyroid hormone excess or deficiency is known to have wide-ranging effects on a variety of organ systems. Our objective is to describe the magnitude, biochemical features, and clinical characteristics of hepatic abnormalities in patients with acute thyrotoxicosis. We performed a retrospective review of all patients admitted to our institution between January 1, 1998 and December 31, 2008 with a discharge diagnosis of acute thyrotoxicosis excluding iatrogenic causes. The records of these patients were reviewed and data extracted regarding demographic, biochemical, and clinical data particularly relevant to liver function. Fourteen patients were identified of which eleven had liver studies performed. The majority (90.9%) had Graves disease. Nine of eleven patients (81.8%) had some degree of hepatic abnormality. Seven patients (63.6%) had an elevation in one or both transaminases, and two (18.2%) had isolated synthetic dysfunction as manifested as an elevated INR and/or decreased albumin without transaminitis. The mean magnitude of deviation from the normal range was greater in the transaminases as compared to bilirubin, INR, or albumin. Definitive treatment was radioiodine ablation in six cases (54.5%) and surgical thyroidectomy in two cases (18.2%). Noniatrogenic acute thyrotoxicosis requiring hospitalization is a rare condition which is most frequently caused by Graves disease. The majority of patients have disordered liver tests of a highly variable nature, making the recognition of this association important in the care of patients presenting with acute thyrotoxicosis. Richard M. Elias, Diana S. Dean, and Gregory W. Barsness Copyright © 2012 Richard M. Elias et al. All rights reserved. Mon, 26 Nov 2012 10:34:09 +0000 http://www.hindawi.com/isrn/endocrinology/2012/237613/ To investigate the effect of acylated ghrelin on the activation of TLR4/NF-κB signaling pathway induced by palmitic acid in human monocyte-derived (THP-1) macrophages, THP-1 macrophages were cultured for 12 h by palmitic acid with various concentrations. The THP-1 macrophages was pretreated by acylated ghrelin at different doses for 4 h before cultivated by palmitic acid (200 μmol/L) for 12 h. We observed the level of TLR4, NF-κB p65 phosphorylation in THP-1 macrophages and TNF-α, IL-1β in culture supernatant. TLR4 mRNA was measured by real-time PCR. TLR4 protein and NF-κB p65 phosphorylation was measured by western blotting. The expression of TNF-α and IL-1β was detected by ELISA. Compared to the THP-1 macrophages without palmitic acid, the level of TLR4 mRNA protein and NF-κB p65 phosphorylation and the expression of TNF-α and IL-1β increased after treatment by palmitic acid in a dose-dependent fashion (). Compared to the THP-1 macrophages with palmitic acid (200 μmol/L), the level of the pervious substances decreased after preadministration by acylated ghrelin in a dose-dependent fashion. So, we make a conclusion that acylated ghrelin can regulate the activation of TLR4/NF-κB signaling pathway and inhibit the release of inflammatory cytokines in THP-1 macrophages which are stimulated by palmitic acid in a dose-dependent fashion. S. P. Liu, X. Y. Li, Z. Li, L. N. He, Y. Xiao, K. Yan, and Z. G. Zhou Copyright © 2012 S. P. Liu et al. All rights reserved.