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Journal of Molecular Endocrinology

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https://www.readbyqxmd.com/read/29678908/the-lim-homeodomain-protein-isl1-mediates-the-function-of-tcf7l2-in-pancreatic-beta-cells
#1
Weijuan Shao, Vivian Szeto, Zhuolun Song, Lili Tian, Zhong-Ping Feng, Cristina M Nostro, Tianru Jin
Pancreatic β-cell Tcf7l2 deletion or its functional knockdown suggested the essential role of this Wnt pathway effector in controlling insulin secretion, glucose homeostasis, and β-cell gene expression. As the LIM homeodomain protein Isl1 is a suggested Wnt pathway downstream target, we hypothesize that it mediates metabolic functions of Tcf7l2. We aimed to determine the role of Isl1 in mediating the function of Tcf7l2 and the incretin hormone GLP-1 in pancreatic β-cells. Effect of dominant negative TCF7L2 (TCF7L2DN) mediated Wnt pathway functional knockdown on Isl1 expression was determined in βTCFDN mouse islets and in the rat insulinoma cell line INS-1 832/13...
April 20, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29661799/the-role-of-beta-cell-heterogeneity-in-islet-function-and-insulin-release
#2
Daniela Nasteska, David Hodson
It is becoming increasingly apparent that not all insulin-secreting beta cells are equal. Subtle differences exist at the transcriptomic and protein expression levels, with repercussions for beta cell survival/proliferation, calcium signalling and insulin release. Notably, beta cell heterogeneity displays plasticity during development, metabolic stress and type 2 diabetes mellitus (T2DM). Thus, heterogeneity or lack thereof may be an important contributor to beta cell failure during T2DM in both rodents and humans...
April 16, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29650721/lect2-promotes-inflammation-and-insulin-resistance-in-adipocytes-via-p38-pathways
#3
Tae Woo Jung, Yoon Hee Chung, Hyoung-Chun Kim, A M Abd El-Aty, Ji Hoon Jeong
Leukocyte cell-derived chemotaxin 2 (LECT2) is a recently identified novel hepatokine that causes insulin resistance in skeletal muscle by activating c-Jun N-terminal kinase (JNK), thereby driving atherosclerotic inflammation. However, the role of LECT2 in inflammation and insulin resistance in adipocytes has not been investigated. In this study, we report that LECT2 treatment of differentiated 3T3-L1 cells stimulates P38 phosphorylation in a dose-dependent manner. LECT2 also enhanced inflammation markers such as IκB phosphorylation, NF-κB phosphorylation, and IL-6 expression...
April 12, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29632026/prolactin-protects-against-cytokine-induced-beta-cell-death-by-nfkb-and-jnk-inhibition
#4
Tarlliza Romanna Nardelli, Emerielle Cristina Vanzela, Keli Cristina Benedicto, Flora Brozzi, André Fujita, Alessandra K Cardozo, Décio Eizirik, Antonio Carlos Boschero, Fernanda Ortis
Type 1 diabetes is caused by an autoimmune assault that induces progressive beta cell dysfunction and dead. Pro-inflammatory cytokines, such as interleukin 1 beta (IL1b), tumor necrosis factor (TNF) and interferon gamma (IFNg) contribute for beta cell death, which involves activation of the nuclear factor kappa B (NFkB) and jun N-terminal kinase (JNK). Prolactin (PRL), a physiological mediator for beta cell proliferation, was shown to protect beta cells against cytokines pro-apoptotic effects. We presently investigated the mechanisms involved in the protective effects of prolactin against cytokine-induced beta cell death...
April 9, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29632025/effects-of-neuromedin-b-on-steroidogenesis-cell-proliferation-and-apoptosis-in-porcine-leydig-cell
#5
Zhiyu Ma, Ying Zhang, Juan Su, Sheng Yang, Wenna Qiao, Xiang Li, Zhihai Lei, Ling Cheng, Na An, Wenshao Wang, Yanyan Feng, Jinlong Zhang
Neuromedin B (NMB), a mammalian bombesin-related peptide, has numerous physiological functions, including regulating hormone secretions, cell growth, and reproduction, by binding to its receptor (NMBR). In this study, we investigated the effects of NMB on testosterone secretion, steroidogenesis, cell proliferation, and apoptosis in cultured primary porcine Leydig cells. NMBR was mainly expressed in the Leydig cells of porcine testes, and a specific dose of NMB significantly promoted the secretion of testosterone in the primary Leydig cells; moreover, NMB increased the expression of mRNA and/or proteins of NMBR and steroidogenic mediators (StAR, CYP11A1, and 3β-HSD) in the Leydig cells...
April 9, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29626053/insulin-like-growth-factors-actions-on-the-skeleton
#6
Shoshana Yakar, Haim Werner, Cliff Rosen
The discovery of the growth hormone (GH)-mediated somatic factors (somatomedins), insulin-like growth factor (IGF)-I and -II, has elicited an enormous interest primarily amongst endocrinologists who study growth and metabolism. The advancement of molecular endocrinology over the past four decades enables investigators to re-examine and refine the established somatomedin hypothesis. Specifically, gene deletions, transgene overexpression, or more recently, cell-specific gene-ablations, have enabled investigators to study the effects of the Igf-I and Igf-II genes in temporal and spatial manners...
April 6, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29618488/steroid-sulfatase-inhibition-by-aryl-sulfamates-clinical-progress-mechanism-and-future-prospects
#7
Barry V L Potter
Steroid sulfatase is an emerging drug target for the endocrine therapy of hormone-dependent diseases, catalyzing estrogen sulfate hydrolysis to estrogen. Drug discovery, developing the core aryl O-sulfamate pharmacophore, has led to steroidal and non-steroidal drugs entering numerous clinical trials, with promising results in oncology and women's health. Steroidal estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors and one was developed clinically as an oral estradiol pro-drug and for endometriosis applications...
April 4, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29615472/epigenetic-regulation-in-the-tumorigenesis-of-men1-associated-endocrine-cell-types
#8
Sucharitha Iyer, Sunita K Agarwal
Epigenetic regulation is emerging as a key feature in the molecular characteristics of various human diseases. Epigenetic aberrations can occur from mutations in genes associated with epigenetic regulation, improper deposition, removal or reading of histone modifications, DNA methylation/demethylation, and impaired non-coding RNA interactions in chromatin. Menin, the protein product of the gene causative for the multiple endocrine neoplasia type 1 (MEN1) syndrome, interacts with chromatin-associated protein complexes and also regulates some non-coding RNAs, thus participating in epigenetic control mechanisms...
April 3, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29599414/insights-into-calcium-sensing-receptor-trafficking-and-biased-signalling-by-studies-of-calcium-homeostasis
#9
Caroline Gorvin
The calcium-sensing receptor (CaSR) is a class C G-protein coupled receptor (GPCR) that detects extracellular calcium concentrations, and modulates parathyroid hormone secretion and urinary calcium excretion to maintain calcium homeostasis. The CaSR utilises multiple heterotrimeric G-proteins to mediate signalling effects including: activation of intracellular calcium release; mitogen-activated protein kinase (MAPK) pathways; membrane ruffling; and inhibition of cAMP production. By studying germline mutations in the CaSR and proteins within its signalling pathway that cause hyper- and hypocalcaemic disorders, novel mechanisms governing GPCR signalling and trafficking have been elucidated...
March 29, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29588428/expression-of-sult2a1-sult2b1-and-hsd3b1-in-the-porcine-testis-and-epididymis
#10
Bettina Zimmer, Linda Tenbusch, Michele C Klymiuk, Yaser Dezhkam, Gerhard Schuler
In the porcine testis in addition to estrogen sulfates the formation of numerous sulfonated neutral hydroxysteroids has been observed. However, their functions and the underlying synthetic pathways are still widely unclear. To obtain further information on their formation in postpubertal boars the expression of sulfotransferases considered relevant for neutral hydroxysteroids (SULT2A1, SULT2B1) was investigated in the testis and defined segments of the epididymis applying real-time RT-qPCR, Western blot and immunohistochemistry (IHC)...
March 27, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29588427/molecular-mechanisms-of-glucocorticoids-on-skeleton-and-regeneration-after-fracture
#11
Yasmine Hachemi, Anna Rapp, Ann-Kristin Picke, Gilbert Weidinger, Anita Ignatius, Jan Tuckermann
Glucocorticoid hormones (GCs) have profound effects on bone metabolism. Via their nuclear hormone receptor - the GR - they act locally within bone cells and modulate their proliferation, differentiation, and cell death. Consequently, high glucocorticoid levels - as present during steroid therapy or stress - impair bone growth and integrity, leading to retarded growth and glucocorticoid-induced osteoporosis, respectively. Because of their profound impact on the immune system and bone cell differentiation, GCs also affect bone regeneration and fracture healing...
March 27, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29588426/potential-benefits-of-a-sulfated-resveratrol-derivative-for-topical-application
#12
Marta Correia-da-Silva, Verónica Rocha, Cláudia Marques, Cláudia Deus, Adriana Marques-Carvalho, Paulo Oliveira, Andreia Palmeira, Madalena Pinto, Maria Emília Sousa, José Sousa Lobo, Isabel Almeida
Resveratrol (RSV) is a polyphenolic compound with antioxidant, anti-inflammatory, and anti-aging properties partly associated with sirtuin-1 (SIRT1)-activation in the skin. However, poor water solubility may limit RSV efficacy. This work aimed to clarify the interest of a new synthetic water-soluble RSV derivative (resveratrol glucoside sulfate, RSV-GS) for topical application. Resveratrol glucoside sulfate was synthesized using microwave-assisted sulfation. Cytotoxicity assays were performed with the keratinocyte HaCaT cell line, using MTT reduction, neutral red uptake, Alamar Blue/resazurin reduction, trypan blue exclusion, and measurement of ATP concentration...
March 27, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29581239/role-of-igf-i-and-efn-eph-signaling-in-skeletal-metabolism
#13
Richard C Lindsey, Charles H Rundle, Subburaman Mohan
Insulin-like growth factor (IGF)-I and ephrin ligand (efn)-receptor (Eph) signaling are both crucial for bone cell function and skeletal development and maintenance. IGF-I signaling is the major mediator of growth hormone-induced bone growth, but a host of different signals and factors regulate IGF-I signaling at the systemic and local levels. Disruption of the Igf1 gene results in reduced peak bone mass in both experimental animal models and humans. Additionally, efn-Eph signaling is a complex system which, particularly through cell-cell interactions, contributes to the development and differentiation of many bone cell types...
March 26, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29581238/role-of-dysfunctional-adipocytes-in-cholesterol-induced-nonobese-metabolic-syndrome
#14
Jiung-Pang Huang, Sheng-Chieh Hsu, Yaa-Jyuhn James Meir, Po-Shiuan Hsieh, Chih-Chun Chang, Kuan-Hsing Chen, Jan-Kan Chen, Li-Man Hung
Many studies have reported the causes of obese metabolic syndrome (MS); however, the causes of nonobese MS (NMS) remain unknown. In this study, we demonstrated that inflamed dysfunctional adipose tissue plays a crucial role in cholesterol-induced NMS. Control (C), high cholesterol (HC), and HC with 10% fructose in drinking water (HCF) diets were fed to Sprague-Dawley rats for 12 weeks. After 12 weeks, the body weights of the C- and HC-fed rats were comparable, but the weights of the HCF-fed rats were relatively low...
March 26, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29563157/role-of-igf-binding-proteins-in-regulating-igf-responses-to-changes-in-metabolism
#15
David Clemmons
The IGF binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF-I and IGF-II. These proteins are present in plasma and extracellular fluids and regulate access of both IGF-I and II to the type I IGF receptor. Additionally they have functions that are independent of their ability to bind IGFs. Each protein is regulated independently of IGF-I and IGF-II and this provides an important mechanism by which other hormones and physiologic variables can regulate IGF actions indirectly...
March 21, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29563156/hepcidin-is-an-endogenous-protective-factor-for-osteoporosis-by-reducing-iron-levels
#16
Peng Zhang, Liang Wang, Sheng Wang, Binchen Shan, Zhiqiang Zhou, Hui Zhang, Fan Yang, Xiao Wang, Ye Yuan, Youjia Xu
Postmenopausal osteoporosis is a global health issue. Although a lack of estrogen is considered the major reason for postmenopausal osteoporosis, other factors might also contribute the etiology of the disease. In previous reports, we and others proposed that iron accumulation after menopause accelerates osteoporosis, and here we genetically modified the expression of an endogenous hormone, hepcidin, to modulate iron status in a mouse model. Our results show that hepcidin levels negatively correlate with bone loss in both knockout and overexpression (with ovariectomy) murine models...
March 21, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29555819/de-scilencing-grb10-contributes-to-acute-er-stress-induced-steatosis-in-mouse-liver
#17
Liping Luo, Wanxiang Jiang, Hui Liu, Jicheng Bu, Ping Tang, Chongyangzi Du, Zhipeng Xu, Hairong Luo, Bilian Liu, Bo Xiao, Zhiguang Zhou, Feng Liu
The growth receptor binding protein Grb10 is an imprinted gene product and a key negative regulator of the insulin, IGF1 and mTORC1 signaling pathways. Grb10 is highly expressed in mouse fetal liver but almost completely silenced in adult mice, suggesting a potential detrimental role of this protein in adult liver function. Here we show that the grb10 gene could be reactivated in adult mouse liver by acute endoplasmic reticulum stress (ER stress) such as tunicamycin or a short-term high fat diet (HFD) challenge, concurrently with increased unfolded protein response (UPR) and hepatosteatosis...
March 19, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29535161/igf-i-receptor-signaling-pathways
#18
Fumihiko Hakuno, Shin-Ichiro Takahashi
Insulin-like growth factors (IGFs) bind specifically to the IGF-I receptor on the cell surface of targeted tissues. Ligand binding to the α subunit of the receptor leads to a conformational change in the β subunit, resulting in the activation of receptor tyrosine kinase activity. Activated receptor phosphorylates several substrates, including insulin receptor substrates (IRSs) and Src-homology collagen (Shc). Phosphotyrosine residues in these substrates are recognized by certain Src homology 2 (SH2) domain containing signaling molecules...
March 13, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29476039/estrogen-induced-inhibition-of-spermatogenesis-in-zebrafish-is-largely-reversed-by-androgen
#19
Luiz Henrique de Castro Assis, Rafael Henrique Nobrega, Nuria Esther Gómez-González, Jan Bogerd, Rüdiger Schulz
The hormonal regulation of spermatogenesis involves both gonadotropins and steroid hormones. Long-term in vivo exposure of adult zebrafish to estrogen impaired spermatogenesis associated with an androgen insufficiency, possibly induced by inhibiting gonadotropin release. Using this experimental model, we investigated if androgen treatment could enhance spermatogenesis, while maintaining the inhibition of gonadotropin release through continued estrogen exposure. Moreover, we also exposed animals to androgen alone, in order to examine androgen effects in the absence of estrogen-induced gonadotropin inhibition...
February 23, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29467141/the-role-of-sirtuin1-ppar%C3%AE-%C3%AF-axis-in-placental-development-and-function
#20
Jonathan Pham, Kanaga Arul Nambi Rajan, Ping Li, Mana M Parast
Placental development is important for proper in utero growth and development of the fetus, as well as maternal well-being during pregnancy. Abnormal differentiation of placental epithelial cells, called trophoblast, is at the root of multiple pregnancy complications, including miscarriage, the maternal hypertensive disorder preeclampsia, and intrauterine growth restriction. The ligand-activated nuclear receptor, PPARγ, and nutrient sensor, Sirtuin-1, both play a role in numerous pathways important to cell survival and differentiation, metabolism, and inflammation...
February 21, 2018: Journal of Molecular Endocrinology
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