ISRN endocrinology最新文献

The polypeptide hormone stanniocalcin-1 (STC-1) is widely expressed in mammals and signals both locally and systemically. In many tissues STC-1 ligand is sequestered by target cell organelles (mitochondria, nuclei, and cholesterol lipid droplets) to exert diverse biological effects. Most notably, STC-1 serves as an uncoupler of oxidative phosphorylation in liver, muscle, and kidney mitochondria. The present paper describes the identification of STC-1 receptors in mouse pancreatic β cells and the discovery that the ligand co-localizes with insulin in pancreatic β cells. In situ hybridization (ISH) analysis subsequently revealed that pancreatic β cells were the source of the ligand. Intriguingly however, all ISH signal was localized over putative islet cell nuclei as opposed to the cell cytoplasm. Real-time qPCR and agarose gel electrophoresis revealed that the STC-1 amplicon generated from islet cell total RNA was the same size as that from kidney. However, relative levels of STC-1 gene expression were >100-fold lower in islets than those in kidney tissue. Collectively, these findings are indicative of a local STC-1 signalling pathway in pancreatic β cells. The role of STC-1 in this context remains to be established, but it could very well entail the regulation of β cell mitochondria membrane potential which is an integral aspect of regulated insulin release. Interestingly, STC-1 immunoreactivity was not evident in embryonic pancreatic islets, suggesting that ligand synthesis may only commence postnatally.

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.

As the worldwide prevalence of type 2 diabetes continues to rise at an alarming rate, the search for susceptible populations likely to benefit from preventative measures becomes more important. One such population is women with a previous history of gestational diabetes mellitus (GDM). In this prospective study of 101 women who had GDM in Australia, ethnicity was a major risk factor for the development of diabetes following a diagnosis of GDM. With a mean followup of 5.5 years after GDM, South Asian women had a significantly higher risk of developing abnormal glucose tolerance (AGT) (69%) than women of all other ethnicities (P < 0.05). The prevalence of diabetes and impaired glucose tolerance was also very high amongst other groups: South East and East Asian (11/27, 41%), Middle-Eastern (8/18, 44%), South European backgrounds (5/12, 42%), and Australian-born women 39% (11/28). A review of the literature supports the role of ethnicity in the development of diabetes amongst these women. These findings have implications for South Asian countries and countries such as Australia where there is a population from diverse ethnic backgrounds and where the implementation of targeted measures to stem the growing tide of diabetes is needed.

Bisphenol A (BPA) is a widely used chemical. We examined the association between urinary BPA levels and obesity in the National Health and Nutritional Examination Survey (NHANES) 2003-2008. The main outcome of interest was obesity defined as (1) body mass index (BMI) ≥ 30 Kg/m(2) and (2) waist circumference (WC) ≥ 102 cm in men and ≥ 88 cm in women. Urinary BPA levels were examined in quartiles. Overall, we observed a positive association between increasing levels of urinary BPA and both measures of obesity, independent of potential confounding factors including, smoking, alcohol consumption, and serum cholesterol levels. Compared to quartile 1 (referent), the multivariate-adjusted odds ratio (95% confidence interval) associated with quartile 4 for BMI-based obesity was 1.69 (1.30-2.20); P-trend < 0.0001 and for WC-based obesity was 1.59 (1.21-2.09); P-trend = 0.0009. This association between BPA and both measures of obesity was consistently present across gender and race-ethnic groups (all P-trend < 0.05). Elevated levels of urinary BPA are associated with measures of obesity independent of traditional risk factors. This association is consistently present across gender and race-ethnic groups. Future prospective studies are needed to confirm or disprove this finding.

The polycystic ovary syndrome (PCOS) is one of the most frequent endocrinopathies in women. Its incidence is assessed at 6-8% of the female population in the reproductive age. It is characterised by oligomenorrhea (Oligo), hyperandrogenism (HA), and the presence of polycystic ovaries (PCOs). Carbohydrate and lipid metabolism is being disturbed in many women with PCOS. The pathogenesis of PCOS is still unexplained. Following the main criteria of diagnosis (Rotterdam Consensus 2003), Dewailly, Welt and Pehlivanov divided the patients with PCOS into 4 phenotype groups: A, B, C, and D. In our studies of 93 patients with PCOS, we found (1) the most frequent appearance (60,2%) of the phenotype A [Oligo + HA + PCO]; (2) an increased androstenedione concentration in a group with HA (A, B, C); (3) an increased HOMA-β and insulin concentration after 30 min an oral 75 g glucose tolerance test (OGTT) in a group of obese women with BMI > 30 kg/m(2); (4) high levels of total testosterone, total cholesterol, and LDL cholesterol concentrations in a group A with classic phenotype of PCOS: Oligo + HA + PCO-increasing the risk of development of cardiovascular diseases, type 2 diabetes, or metabolic syndrome. The average androstenedione concentrations could be a good diagnostic and prognostic parameter.

Aim. At present, little data exist about incidence and the risk factors associated with metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2DM). The objectives of present study were to assess the incidence and risk factors of MetS in people with T2DM. Methods. During the mean (SD) follow-up period of 11.7 (4.8) years, 3,047 patients with T2DM and free of MetS at baseline have been examined to determine incidence and predictors of progression to MetS. A modified the National Cholesterol Education Program-Adult Treatment Panel III definition with body mass index (BMI) instead of waist circumference was used for the MetS. Results. The prevalence of MetS was 63.2% (95% CI: 62.3, 64.1). The incidence of MetS was 28.5 (95% CI: 26.8, 30.2) (25.9 men and 30.9 women) per 1,000 patient-years based on 35,677 patient-years of follow-up. Multivariate analysis revealed that higher BMI and education, lower HbA(1c) and treatment with oral agent or insulin were associated with MetS. Conclusion. These are the first estimate of incidence and risk factors of MetS in patients with T2DM in Iran. These findings showed that the natural course of MetS is dynamic. The clinical management of patients with T2DM will contribute significantly to MetS prevention.

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 (P < 0.05). 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.

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 (P < 0.05) and total power (P < 0.01) was observed in T2DM. CIMT and CAC scores were significantly higher while FMD was significantly lower in diabetics (P < 0.01 for all). Median HbA(1c) levels were significantly higher in diabetics. CIMT was inversely and independently associated with total power both in diabetics and controls (P < 0.01 for both groups). There was also an inverse association between total power and median HbA(1c). 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.

The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration.

The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.