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Journal of Endocrinology

Andrew W Norris, Katie Larson Ode, Lina Merjaneh, Srinath Sanda, Yaling Yi, Xingshen Sun, John F Engelhardt, Rebecca L Hull
In cystic fibrosis (CF), ductal plugging and acinar loss result in rapid decline of exocrine pancreatic function. This destructive process results in remodeled islets, with only a modest reduction in insulin producing β cells. However, β-cell function is profoundly impaired, with decreased insulin release and abnormal glucose tolerance being present even in infants with CF. Ultimately, roughly half of CF subjects develop diabetes (termed CF-related diabetes, CFRD). Importantly, CFRD increases CF morbidity and mortality via worsening catabolism and pulmonary disease...
February 1, 2019: Journal of Endocrinology
Anna Edlund, Mohammad Barghouth, Michael Huhn, Mia Abels, Jonathan Esguerra, Ines Mollet, Emma Svedin, Anna Wendt, Erik Renstrom, Enming Zhang, Nils Wierup, Bob J Scholte, Malin Flodström-Tullberg, Lena Eliasson
Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The cause of CFRD is unclear, but a commonly observed reduction in first-phase insulin secretion suggests defects at the beta cell level. Here we aimed to examine beta- and alpha-cell function in the Cftrtm1EUR/F508del mouse model (C57BL/6J), which carries the most common human mutation in CFTR, the F508del mutation...
February 1, 2019: Journal of Endocrinology
Tom Nicholson, Chris Church, Kostas Tsintzas, Robert Jones, Leigh Breen, Edward T Davis, David J Baker, Simon W Jones
Adipokines have emerged as central mediators of insulin sensitivity and metabolism, in part due to the known association of obesity with metabolic syndrome disorders such as type 2 diabetes. Recent studies in rodents have identified the novel adipokine vaspin, as playing a protective role in inflammatory metabolic diseases by functioning to promote insulin sensitivity during metabolic stress. However, at present the skeletal muscle and adipose tissue expression of vaspin in humans is poorly characterised. Furthermore, the functional role of vaspin in skeletal muscle insulin sensitivity has not been studied...
February 1, 2019: Journal of Endocrinology
Miguel A Velazquez, Tom Fleming, Adam J Watkins
The concept emerging from Professor David Barker's seminal research on the developmental origins of later life disease has progressed in many directions since first published. One critical question is when during gestation might environment alter the developmental programme with such enduring consequences. Here, we review the growing consensus from clinical and animal research that the period around conception, embracing gamete maturation and early embryogenesis, might be the most vulnerable period. We focus on four types of environmental exposure shown to modify periconceptional reproduction and offspring development and health: maternal overnutrition and obesity; maternal undernutrition; paternal diet and health; and assisted reproductive technology...
February 1, 2019: Journal of Endocrinology
ELizabeth K Fletcher, Monica Kanki, James Morgan, David W Ray, Lea Delbridge, Peter James Fuller, Colin D Clyne, Morag Young
We previously identified a critical pathogenic role for MR activation in cardiomyocytes that included a potential interaction between the MR and the molecular circadian clock. While glucocorticoid regulation of the circadian clock is undisputed, MR interactions with circadian clock signalling are limited. We hypothesised that the MR influences cardiac circadian clock signalling, and vice versa. 10nM aldosterone or corticosterone regulated CRY 1, PER1, PER2 and ReverbA (NR1D1) gene expression patterns in H9c2 cells over 24hr...
January 1, 2019: Journal of Endocrinology
Jirapas Sripetchwandee, Hiranya Pintana, Piangkwan Sa-Nguanmoo, Chiraphat Boonnag, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn
Obese-insulin resistance following chronic high-fat diet consumption led to cognitive decline through several mechanisms. Moreover, sex hormone deprivation, including estrogen and testosterone, could be a causative factor in inducing cognitive decline. However, comparative studies on the effects of hormone-deprivation on the brain are still lacking. Adult Wistar rats from both genders were conducted sham operations or orchiectomies/ovariectomies and given a normal diet or high-fat diet for 4, 8, and 12 weeks...
January 1, 2019: Journal of Endocrinology
Trassanee Chatmethakul, Robert D Roghair
Consistent with the paradigm shifting observations of David Barker and colleagues that revealed a powerful relationship between decreased weight through 2 years of age and adult disease, intrauterine growth restriction (IUGR) and preterm birth are independent risk factors for the development of subsequent hypertension. Animal models have been indispensable in defining the mechanisms responsible for these associations and the potential targets for therapeutic intervention. Among the modifiable risk factors, micronutrient deficiency, physical immobility, exaggerated stress hormone exposure and deficient trophic hormone production are leading candidates for targeted therapies...
January 1, 2019: Journal of Endocrinology
Jin Yu, Yuhuan Yang, Danying Zhang, Dongxia Zhai, Linyi Song, Zailong Cai, Chaoqin Yu
High androgen levels in patients suffering from polycystic ovary syndrome (PCOS) can be effectively reversed if the herb Scutellaria baicalensis is included in traditional Chinese medicine prescriptions. To characterize the effects of baicalin, extracted from S. baicalensis, on androgen biosynthesis in NCI-H295R cells and on hyperandrogenism in PCOS model rats and to elucidate the underlying mechanisms. The optimum concentration and intervention time for baicalin treatment of NCI-H295R cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and enzyme-linked immunosorbent assays...
January 1, 2019: Journal of Endocrinology
Yoko Yagishita, Akira Uruno, Dionysios V Chartoumpekis, Thomas W Kensler, Masayuki Yamamoto
The transcription factor Nrf2 (NF-E2-related factor 2) plays a critical role in oxidative stress responses. While activation of Nrf2 signaling is known to exert anti-inflammatory effects, Nrf2 function in inflammation-mediated autoimmune disorders, such as type 1 diabetes, is not well established. To address the roles of Nrf2 in protection against autoreactive T-cell-induced type 1 diabetes, we used non-obese diabetic (NOD) mice, a polygenic model of human type 1 diabetes, to generate a genetic model that allowed us to assess the contribution of Nrf2 activation to preventing and/or treating type 1 diabetes...
January 1, 2019: Journal of Endocrinology
Jia Sun, Haiping Zhu, Xiaorong Wang, Qiuqi Gao, Zhuoying Li, Huiya Huang
The molecular signaling mechanisms of Coenzyme Q10 (CoQ10) in diabetic nephropathy (DN) remain poorly understood. We verified that mitochondrial abnormalities, like defective mitophagy, the generation of mitochondrial reactive oxygen species (mtROS) and the reduction of mitochondrial membrane potential, occurred in the glomerulus of db/db mice, accompanied by reduced PINK and parkin expression and increased apoptosis. These changes were partially reversed following oral administration of CoQ10. In inner fenestrated murine glomerular endothelial cells (mGECs), high glucose (HG) also resulted in deficient mitophagy, mitochondrial dysfunction and apoptosis, which were reversed by CoQ10...
January 1, 2019: Journal of Endocrinology
Maria F Heber, Silvana R Ferreira, Giselle Adriana Abruzzese, Trinidad Raices, Omar Pedro Pignataro, Margarita Vega, Alicia B Motta
Insulin resistance is the decreased ability of insulin to mediate metabolic actions. In the ovary, insulin controls ovulation and oocyte quality. Alterations in ovarian insulin signaling pathway could compromise ovarian physiology. Here, we aimed to investigate the effects of fetal programming on ovarian insulin signaling and evaluate the effect of metformin treatment. Pregnant rats were hyperandrogenized with testosterone and female offspring born to those dams were employed; at adulthood, prenatally hyperandrogenized (PH) offspring presented two phenotypes: irregular ovulatory (PHiov) and anovulatory (PHanov)...
January 1, 2019: Journal of Endocrinology
Apiwan Arinno, Nattayaporn Apaijai, Puntarik Kaewtep, Wasana Pratchayasakul, Thidarat Jaiwongkam, Sasiwan Kerdphoo, Siriporn Chattipakorn, Nipon Chattipakorn
Although a physiological dose of testosterone replacement therapy (p-TRT) has been shown to improve left ventricular (LV) function, some studies reported that it increased the risk of myocardial infarction in testosterone-deprived men. We previously reported that vildagliptin might be used as an alternative to the p-TRT. In this study, we hypothesized that a combined low-dose TRT with vildagliptin exerts greater efficacy than single regimen in improving cardiometabolic function in obese-insulin resistant rats with testosterone deprivation...
January 1, 2019: Journal of Endocrinology
Jacqueline M Wallace
The competition for nutrients that arises when pregnancy coincides with continuing or incomplete growth in young adolescent girls increases the risk of preterm delivery and low birthweight with negative after-effects for mother and child extending beyond the perinatal period. Sheep paradigms involving nutritional management of weight and adiposity in young biologically immature adolescents have allowed the consequences of differential maternal growth status to be explored. Although nutrient reserves at conception play a modest role, it is the dietary manipulation of the maternal growth trajectory thereafter which has the most negative impact on pregnancy outcome...
January 1, 2019: Journal of Endocrinology
Sui-Lin Sun, Liang-Ming Liu
Urotensin II (UII) is a polypeptide molecule with neurohormone-like activity. It has been confirmed that UII is widely distributed in numerous organs of different animal species from fish to mammals, including humans. The UII receptor is orphan G-protein coupled receptor 14, also known as UT. The tissue distribution of UII and UT is highly consistent, and their expression may be regulated by autocrine and paracrine mechanisms. In the body, UII has many physiological and pathophysiological activities, such as vasoconstrictor and vasodilatory actions, cell proliferation, pro-fibrosis, neuroendocrine activity, insulin resistance, and carcinogenic and inflammatory effects, which have been recognized only in recent years...
January 1, 2019: Journal of Endocrinology
Weiwei Xu, Jamie Morford, Franck Mauvais-Jarvis
One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose homeostasis by testosterone in male and females. Severe testosterone deficiency predisposes men to type 2 diabetes (T2D), while in contrast, androgen excess predisposes women to hyperglycemia. The role of androgen deficiency and excess in promoting visceral obesity and insulin resistance in men and women respectively is well established. However, although it is established that hyperglycemia requires β cell dysfunction to develop, the role of testosterone in β cell function is less understood...
January 1, 2019: Journal of Endocrinology
Yuxun Zhou, Li Tong, Maochun Wang, Xueying Chang, Sijia Wang, Kai Li, Junhua Xiao
Puberty onset is a complex trait regulated by multiple genetic and environmental factors. In this study, we narrowed a puberty related QTL region down to a 1.7 Mb region on chromosome X in female mice and inferred miR-505-3p as the functional gene. We conducted ectopic expression of miR-505-3p in the hypothalamus of prepubertal female mice through lentivirus-mediated orthotopic injection. The impact of miR-505-3p on female puberty was evaluated by the measurement of pubertal/reproduction events and histological analysis...
December 1, 2018: Journal of Endocrinology
Jose Jaime Casasnovas, Yunhee Jo, Xi Rao, Xiaoling Xuei, Mary E Brown, Kok Lim Kua
Offspring of diabetic mothers are susceptible to developing type 2 diabetes due to pancreatic islet dysfunction. However, the initiating molecular pathways leading to offspring pancreatic islet dysfunction are unknown. We hypothesized that maternal hyperglycemia alters offspring pancreatic islet transcriptome and negatively impacts offspring islet function. We employed an infusion model capable of inducing localized hyperglycemia in fetal rats residing in the left uterine horn, thus avoiding other factors involved in programming offspring pancreatic islet health...
December 1, 2018: Journal of Endocrinology
Miriam Thomalla, Andreas Schmid, Elena Neumann, Petra Ina Pfefferle, Ulf Mueller-Ladner, Andreas Schäffler, Thomas Karrasch
Adipocytes express various pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs) and actively participate in anti-bacterial and anti-viral host defence. Obesity is associated with adipose tissue PRR expression. The potential role of Toll-like receptor 9 (TLR9) in adipocytes has not yet been investigated. Here, we evaluated TLR9 expression during adipocyte differentiation (AD) of 3T3-L1 adipocytes, in primary murine adipocytes and in different murine and human adipose tissue depots by real-time PCR, immunocytochemistry and immunohistochemistry...
December 1, 2018: Journal of Endocrinology
Gislaine Almeida-Pereira, Tatiane Vilhena-Franco, Ricardo Coletti, Susana Quirós Cognuck, Hellen Veida Paraguassu Silva, Lucila Leico Kagohara Elias, José Antunes-Rodrigues
17β-Estradiol (E2) has been shown to modulate the renin-angiotensin system in hydromineral and blood pressure homeostasis mainly by attenuating angiotensin II (ANGII) actions. However, the cellular mechanisms of the interaction between E2 and angiotensin II (ANGII) and its physiological role are largely unknown. The present experiments were performed to better understand the interaction between ANGII and E2 in body fluid control in female ovariectomized (OVX) rats. The present results are the first to demonstrate that PKC/p38 MAPK signaling is involved in ANGII-induced water and sodium intake and oxytocin (OT) secretion in OVX rats...
December 1, 2018: Journal of Endocrinology
L Francisco Lorenzo-Martín, Mauricio Menacho-Márquez, Salvatore Fabbiano, Omar Al-Massadi, Antonio Abad, Sonia Rodríguez-Fdez, María A Sevilla, María J Montero, Carlos Diéguez, Rubén Nogueiras, Xosé R Bustelo
Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological and metabolic homeostasis. Using Vav3-deficient mice as a model for chronic sympathoexcitation-associated disorders, we report here that afferent fibers of the hepatic branch of the vagus nerve are needed for the development of the peripheral sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis and adipose tissue thermogenesis present in those mice. This neuronal pathway contributes to proper activity of the rostral ventrolateral medulla, a sympathoregulatory brainstem center hyperactive in Vav3-/- mice...
March 1, 2019: Journal of Endocrinology
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