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Therapeutic Approaches to Preserve Islet Mass in Type 2 Diabetes
24 Dec 2005 16:24 AR ANRV262-ME57-17.tex XMLPublishSM(2004/02/24) P1: OJO 10.1146/annurev.med.57.110104.115624 Annu. Rev. Med. 2006. 57:265–81 doi: 10.1146/annurev.med.57.110104.115624 Copyright c 2006 by Annual Reviews. All rights reserved THERAPEUTIC APPROACHES TO PRESERVE ISLET MASS IN TYPE 2DIABETES Laurie L. Baggio and Daniel J. Drucker Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Center, University of Toronto, Toronto, Ontario, Canada M5S 2S2; email: [email protected] KeyWords β-cell mass, apoptosis, neogenesis, proliferation ■ Abstract Type 2 diabetes is characterized by hyperglycemia resulting from in- sulin resistance in the setting of inadequate β-cell compensation. Currently available therapeutic agents lower blood glucose through multiple mechanisms but do not directly reverse the decline in β-cell mass. Glucagon-like peptide-1 (GLP-1) receptor agonists, exemplified by Exenatide (exendin-4), not only acutely lower blood glucose but also engage signaling pathways in the islet β-cell that lead to stimulation of β-cell repli- cation and inhibition of β-cell apoptosis. Similarly, glucose-dependent insulinotropic polypeptide (GIP) receptor activation stimulates insulin secretion, enhances β-cell proliferation, and reduces apoptosis. Moreover, potentiation of the endogenous post- prandial levels of GLP-1 and GIP via inhibition of dipeptidyl peptidase-IV (DPP-IV) also expands β-cell mass via related mechanisms. The thiazolidinediones (TZDs) en- hance insulin sensitivity, reduce blood glucose levels, and also preserve β-cell mass, although it remains unclear whether TZDs affect β-cell mass via direct mechanisms. Complementary approaches to regeneration of β-cell mass involve combinations of factors, exemplified by epidermal growth factor and gastrin, which promote islet neo- genesis and ameliorate diabetes in rodent studies. -
Strategies to Increase ß-Cell Mass Expansion
This electronic thesis or dissertation has been downloaded from the King’s Research Portal at https://kclpure.kcl.ac.uk/portal/ Strategies to increase -cell mass expansion Drynda, Robert Lech Awarding institution: King's College London The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without proper acknowledgement. END USER LICENCE AGREEMENT Unless another licence is stated on the immediately following page this work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence. https://creativecommons.org/licenses/by-nc-nd/4.0/ You are free to copy, distribute and transmit the work Under the following conditions: Attribution: You must attribute the work in the manner specified by the author (but not in any way that suggests that they endorse you or your use of the work). Non Commercial: You may not use this work for commercial purposes. No Derivative Works - You may not alter, transform, or build upon this work. Any of these conditions can be waived if you receive permission from the author. Your fair dealings and other rights are in no way affected by the above. Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 Strategies to increase β-cell mass expansion A thesis submitted by Robert Drynda For the degree of Doctor of Philosophy from King’s College London Diabetes Research Group Division of Diabetes & Nutritional Sciences Faculty of Life Sciences & Medicine King’s College London 2017 Table of contents Table of contents ................................................................................................. -
Redirecting Intracellular Trafficking and the Secretion Pattern of FSH Dramatically Enhances Ovarian Function in Mice
Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice Huizhen Wanga, Melissa Larsona, Albina Jablonka-Shariffb, Christopher A. Pearlb, William L. Millerc, P. Michael Connd, Irving Boimeb, and T. Rajendra Kumara,e,1 Departments of aMolecular and Integrative Physiology and ePathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160; bDepartment of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110; cDepartment of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695; and dDepartments of Internal Medicine and Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430 Edited by R. Michael Roberts, University of Missouri, Columbia, MO, and approved February 28, 2014 (received for review November 14, 2013) FSH and luteinizing hormone (LH) are secreted constitutively or in Results pulses, respectively, from pituitary gonadotropes in many vertebrates, Strategy to Redirect FSH from the Constitutive to Regulated Pathway. Our and regulate ovarian function. The molecular basis for this evolution- in vitro screens indicated that a carboxyterminal (C′)-heptapeptide arily conserved gonadotropin-specific secretion pattern is not un- in the human LHβ (LSGLLFL) (12) or a modified FSHβ con- derstood. Here, we show that the carboxyterminal heptapeptide in taining this peptide (13) favors secretion of corresponding dimers LH is a gonadotropin-sorting determinant in vivo that directs pulsatile via the regulated pathway in heterologous somatotrope cells. secretion. FSH containing this heptapeptide enters the regulated Based on these initial data, we engineered human transgenes en- pathway in gonadotropes of transgenic mice, and is released in β ′ response to gonadotropin-releasing hormone, similar to LH. -
Dynamic Gnrh and Hcg Testing: Establishment of New Diagnostic Reference Levels
176:4 PROOF ONLY A K Bang and others Reference levels on GnRH and 176:4 379–391 Clinical Study hCG tests Dynamic GnRH and hCG testing: establishment of new diagnostic reference levels A Kirstine Bang1,2, Loa Nordkap1,2, Kristian Almstrup1,2, Lærke Priskorn1,2, Jørgen Holm Petersen1,2,3, Ewa Rajpert-De Meyts1,2, Anna-Maria Andersson1,2, Anders Juul1,2 and Niels Jørgensen1,2 1Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Correspondence Denmark, 2International Center for Research and Research Training in Endocrine Disruption of Male should be addressed Reproduction and Child Health (EDMaRC), Rigshospitalet, Denmark, and 3Department of Biostatistics, to N Jørgensen University of Copenhagen, Copenhagen, Denmark Email [email protected] Abstract Objective: Gonadotropin-releasing hormone (GnRH) and human chorionic gonadotropin (hCG) stimulation tests may be used to evaluate the pituitary and testicular capacity. Our aim was to evaluate changes in follicular-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone after GnRH and hCG stimulation in healthy men and assess the impact of six single nucleotide polymorphisms on the responses. Design: GnRH and hCG stimulation tests were performed on 77 healthy men, 18–40 years (reference group) at a specialized andrology referral center at a university hospital. The potential influence of the tests was illustrated by results from 45 patients suspected of disordered hypothalamic–pituitary–gonadal axis. Methods: Baseline, stimulated, relative and absolute changes in serum FSH and LH were determined by ultrasensitive TRIFMA, and testosterone was determined by LC–MS/MS. Results: For the reference group, LH and FSH increased almost 400% and 40% during GnRH testing, stimulated levels varied from 4.4 to 58.8 U/L and 0.2 to 11.8 U/L and FSH decreased in nine men. -
Interleukin 6 Inhibits Mouse Placental Lactogen II but Not Mouse Placental Lactogen I Secretion in Vitro (Trophoblast/Pregnancy/Cytokine) M
Proc. Natl. Acad. Sci. USA Vol. 90, pp. 11905-11909, December 1993 Physiology Interleukin 6 inhibits mouse placental lactogen II but not mouse placental lactogen I secretion in vitro (trophoblast/pregnancy/cytokine) M. YAMAGUCHI*t, L. OGREN*, J. N. SOUTHARD*, H. KURACHI*, A. MIYAKEt, AND F. TALAMANTES*§ *Department of Biology, University of California, Santa Cruz, CA 95064; and tDepartment of Obstetrics and Gynecology, Osaka University Medical School, Osaka, Japan 565 Communicated by George E. Seidel, Jr., September 7, 1993 (receivedfor review June 9, 1993) ABSTRACT The mouse placenta produces several poly- members ofthe PRL-GH gene family. We have used primary peptides belonging to the prolactin-growth hormone gene fam- cultures of placental cells from several days of pregnancy to ily, including mouse placental lactogen (mPL) I and mPL-II. demonstrate that IL-6 regulates the secretion of mPL-II, but The present study was undertaken to determine whether the not mPL-I, and that the sensitivity of mPL-II secretion to secretion of mPL-I and mPL-H is regulated by interleukin 6 IL-6 varies during gestation. (IL-6), which is present in the placenta and has previously been reported to stimulate the secretion ofpituitary members of this gene family. Effects of human and mouse IL-6 on mPL-I and MATERIALS AND METHODS mPL-II secretion were examined in primary cultures of pla- Hormones, Cytokines, and Antisera. mPL-II and recombi- cental cells from days 7, 9, and 12 of pregnancy. IL-6 caused nant mPL-I were purified as described (10, 16). Rabbit a dose-dependent reduction in the mPL-HI concentration in the anti-mPL-I and rabbit anti-mPL-II antisera have been de- medium of cells from days 9 and 12 of pregnancy but did not scribed (11, 16). -
Placental Growth Hormone-Related Proteins and Prolactin-Related Proteins
Placental Growth Hormone-Related Proteins and Prolactin-Related Proteins The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Haig, D. 2008. Placental growth hormone-related proteins and prolactin-related proteins. Placenta 29: 36-41. Published Version doi:10.1016/j.placenta.2007.09.010 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:11148777 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Placental growth hormone-related proteins and prolactin-related proteins. David Haig Department of Organismic and Evolutionary Biology, Harvard University, 26 Oxford Street, Cambridge MA 02138. e-mail: [email protected] phone: 617-496-5125 fax: 617-495-5667 Keywords: GH, PRL, placenta, endometrial glands, placental lactogen The placentas of ruminants and muroid rodents express prolactin (PRL)-related genes whereas the placentas of anthropoid primates express growth hormone (GH)-related genes. The evolution of placental expression is associated with acclerated evolution of the corresponding pituitary hormone and destabilization of conserved endocrine systems. In particular, placental hormones often evolve novel interactions with new receptors. The adaptive functions of some placental hormones may be revealed only under conditions of physiological stress. Introduction Placental hormones are produced by offspring, but act on receptors of mothers. As such, placental hormones and maternal receptors are prime candidates for the expression of parent-offspring conflict [1,2]. -
Maternal Adiponectin Prevents Visceral Adiposity and Adipocyte Hypertrophy in Prenatal Androgenized Female Mice
Received: 25 September 2020 | Revised: 26 November 2020 | Accepted: 7 December 2020 DOI: 10.1096/fj.202002212R RESEARCH ARTICLE Maternal adiponectin prevents visceral adiposity and adipocyte hypertrophy in prenatal androgenized female mice Yanling Wu1 | Belén Chanclón1 | Peter Micallef1 | qElisabet Stener-Victorin2 | Ingrid Wernstedt Asterholm1 | Anna Benrick1,3 1Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Abstract Academy, University of Gothenburg, Hyperandrogenism is the main characteristic of polycystic ovary syndrome, which Gothenburg, Sweden affects placental function and fetal growth, and leads to reproductive and metabolic 2 Department of Physiology and dysfunction in female offspring. Adiponectin acts on the placenta and may exert Pharmacology, Karolinska Institute, Stockholm, Sweden endocrine effects on the developing fetus. This study aims to investigate if mater- 3School of Health Sciences, University of nal and/or fetal adiponectin can prevent metabolic and reproductive dysfunction in Skövde, Skövde, Sweden prenatal androgenized (PNA) female offspring. Adiponectin transgenic (APNtg) and wild-type dams received dihydrotestosterone/vehicle injections between gesta- Correspondence Anna Benrick, Department of Physiology, tional days 16.5-18.5 to induce PNA offspring, which were followed for 4 months. University of Gothenburg, Institute of Offspring from APNtg dams were smaller than offspring from wild-type dams, in- Neuroscience and Physiology, Box 423, 405 30 Gothenburg, Sweden. dependent of genotype. Insulin sensitivity was higher in wild-type mice from APNtg Email: [email protected] dams compared to wild-types from wild-type dams, and insulin sensitivity correlated with fat mass and adipocyte size. PNA increased visceral fat% and adipocyte size in Funding information Novo Nordisk Fonden (NNF), Grant/ wild-type offspring from wild-type dams, while wild-type and APNtg offspring from Award Number: NNF19OC0056601; APNtg dams were protected against this effect. -
Follicle-Stimulating Hormone Regulates Expression and Activity of Epidermal Growth Factor Receptor in the Murine Ovarian Follicle
Follicle-stimulating hormone regulates expression and activity of epidermal growth factor receptor in the murine ovarian follicle Stephany El-Hayeka,b,c, Isabelle Demeesterea,c,d, and Hugh J. Clarkea,b,c,e,1 Departments of aObstetrics and Gynecology, bBiology, and eMedicine, McGill University, Montreal, QC, Canada H3A 1A1; cResearch Institute–McGill University Health Centre; Montreal, QC, Canada H3A 1A1; and dResearch Laboratory on Human Reproduction Fertility Clinic, Université Libre de Bruxelles Erasme, 1070 Brussels, Belgium Edited by John J. Eppig, The Jackson Laboratory, Bar Harbor, ME, and approved October 21, 2014 (received for review August 4, 2014) Fertility depends on the precise coordination of multiple events view that the EGFR signaling mediates many or most ovulatory within the ovarian follicle to ensure ovulation of a fertilizable egg. events. First, the release of the EGFR ligands follows the LH surge FSH promotes late follicular development, including expression of but precedes the LH-dependent responses (9–11). Second, EGF luteinizing hormone (LH) receptor by the granulosa cells. Expres- and the EGFR ligands can induce cumulus expansion and oocyte sion of its receptor permits the subsequent LH surge to trigger the maturation in vitro, independently of LH (9, 10, 20, 29). Third, release of ligands that activate EGF receptors (EGFR) on the gran- these events are impaired in mice bearing a hypomorphic Egfr allele ulosa, thereby initiating the ovulatory events. Here we identify a previously unknown role for FSH in this signaling cascade. We that reduces EGFR activity by about one-half and in mice in which show that follicles of Fshb−/− mice, which cannot produce FSH, Egfr has been selectively inactivated in GCs through a targeted have a severely impaired ability to support two essential EGFR- mutation (22, 23). -
The Importance of Determining Human
JMB 2009; 28 (2) DOI: 10.2478/v10011-009-0003-1 UDK 577.1 : 61 ISSN 1452-8258 JMB 28: 97–100, 2009 Original paper Originalni nau~ni rad THE IMPORTANCE OF DETERMINING HUMAN PLACENTAL LACTOGEN IN THE THIRD TRIMESTER OF PREGNANCY ZNA^AJ ODRE\IVANJA HUMANOG PLACENTALNOG LAKTOGENA U TRE]EM TRIMESTRU TRUDNO]E Jasmina Durkovi}1, Bojana Mandi}2 1Department of Genetics , Town Hospital, Subotica, Serbia 2Mega Lab, Biochemical Laboratory, Subotica, Serbia Summary: Human placental lactogen (HPL) is a hormone Kratak sadr`aj: Humani placentalni laktogen (HPL) jeste produced by the placenta with a role in the re gu lation of hormon koji izlu~uje placenta i regulator je fetoplacen- fetoplacental growth. In this paper, the results of HPL de- talnog rasta. U radu su prikazani rezultati odre|ivanja HPL- termination in the third trimester of pregnancy are pre- a u tre}em trimestru trudno}e, sa ciljem da se ispita senzi - sented with the aim of testing the sensitivity of this bio - tivnost tog biohemijskog markera za otkrivanje poreme}aja chemical marker for detecting placental dysfunction, fetal funkcije placente, vitaliteta fetusa i rizika za lo{ ishod. vitality and risk of bad outcome. The tests were performed Ispitivanje je obavljeno na uzorku od 370 rizi~nih trudno}a on 370 women with high-risk pregnancy, between the 20th izme|u 20 i 36 nedelje trudno}e. HPL je odre|en ELISA and 36th week of pregnancy. HPL was determined by an metodom, testovima »Bioserv Diagnostics«, a rezultati su ELISA method using Bioserv Diagnostics tests and the o~itani na rideru »STAT–FAX 303+«. -
An Exploration of Non-Coding RNA in Exosomes Delivered by Swine Anterior Pituitary
An exploration of non-coding RNA in exosomes delivered by swine anterior pituitary Jiali Xiong South China Agricultural University Haojie Zhang South China Agricultural University Bin Zeng South China Agricultural University Jie Liu South China Agricultural University Junyi Luo South China Agricultural University Ting Chen South China Agricultural University Jiajie Sun South China Agricultural University Qianyun Xi South China Agricultural University Yong-Liang Zhang ( [email protected] ) South China Agricultural University Research article Keywords: Anterior pituitary exosomes, MiRNA, LncRNA, CircRNA, Cross-talk Posted Date: July 29th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-36112/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/26 Abstract Background: The anterior pituitary is a key endocrine organ both in animal and human being drawing much concern. Exosomes are extracellular secretory vesicles carrying proteins, lipids and small RNAs. Previous studies have demonstrated that they had regulatory function both physiologically and pathologically. However, information on exosomes from anterior pituitary remains unknown. Results: In this study, we separated and identied exosomes from anterior pituitary of Duroc swine model for the rst time. Total RNA was extracted and RNA-seq was performed, followed by a comprehensive analysis of miRNAs, lncRNAs and circRNAs. Resultantly, we obtained 343 known miRNAs and 73 novel miRNAs, 15545 lncRNAs and 494 circRNAs. Furthermore, GO and KEGG enrichment analysis showed that the ncRNAs in exosomes may participate in regulating intracellular signal transduction, cellular component organization or biogenesis, small molecule binding, transferase activity. The cross-talk between them also suggested that they may play an important role in signaling process and the biological regulation. -
Single Cell Transcriptomic Analysis of the Adult Mouse Pituitary Reveals a Novel Multi-Hormone Cell Cluster and Physiologic Demand-Induced Lineage Plasticity
bioRxiv preprint doi: https://doi.org/10.1101/475558; this version posted November 22, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Single cell transcriptomic analysis of the adult mouse pituitary reveals a novel multi-hormone cell cluster and physiologic demand-induced lineage plasticity Yugong Ho1,5,*. Peng Hu1,3,5, Michael T. Peel1, Pablo G. Camara1,4, Hao Wu1,3,* , and Stephen A. Liebhaber1,2, Departments of Genetics1 and Medicine2, Penn Epigenetics Institute3, and Penn Institute for Biomedical Informatics4, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 5 These authors contributed equally * Corresponding authors Running title: Single cell transcriptomic analysis of the adult mouse pituitary 1 bioRxiv preprint doi: https://doi.org/10.1101/475558; this version posted November 22, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract The anterior pituitary gland drives a set of highly conserved physiologic processes in mammalian species. These hormonally-controlled processes are central to somatic growth, pubertal transformation, fertility, lactation, and metabolism. Current models, based on targeted immuno-histochemical and mRNA analyses, suggest that each of the seven hormones synthesized by the pituitary is produced by a specific and exclusive cell lineage. However, emerging evidence suggests a more complex model in which critical aspects of hormone specificity and plasticity of pituitary cells remain undefined. Here we have applied massively parallel single-cell RNA sequencing (scRNA-seq), in conjunction with a set of orthogonal imaging studies, to systematically map the cellular composition of adult male and female mouse pituitaries at single-cell resolution and in the setting of major physiologic demands. -
The Endocrine Function of the Placenta: Interactions Between Trophic Peptides and Hormones
Placenlal Function and Fetal Nutrition, edited by Frederick C. Battaglia, Nestle Nutrition Workshop Series. Vol. 39. Nestec Ltd.. Vevey/Lippincott-Raven Publishers. Philadelphia. © 1997. The Endocrine Function of the Placenta: Interactions Between Trophic Peptides and Hormones Lise Cedard U. 361 INSERM, Maternite Baudelocque, 121 Boulevard de Port-Royal Paris, France The placenta is classically considered to be a source of hormones that play an important role in the establishment and maintenance of pregnancy. Because of its hemochorial structure, the human placenta produces hormones and easily secretes them into the maternal circulation. They include steroid hormones, such as estrogens and progesterone, and protein hormones, the most important of which are the chori- onic gonadotrophins (hCG), discovered in 1927. During the period from 1960 to 1980, the concept of a fetoplacental unit (1) with a complementary role for the fetus in steroid production offered a new approach to steroid metabolism, and since then new proteins and neuropeptides have been discovered (2,3). However, the lack of innervation of placental tissue highlights the importance of understanding neuroen- docrine regulation of placental physiology. Sophisticated culture methods enabling the study of biologic phenomena occurring during transformation of cytotrophoblast cells into a syncytiotrophoblast (4) have been combined with electron microscopy and histochemistry. Possibilities offered by molecular biology, including in situ hybridization and molecular cloning studies,