Pregnancy and Human Development from Egg to Embryo
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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 ................................................................................................. -
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]. -
Pathophysiology of Gestational Diabetes Mellitus: the Past, the Present and the Future
6 Pathophysiology of Gestational Diabetes Mellitus: The Past, the Present and the Future Mohammed Chyad Al-Noaemi1 and Mohammed Helmy Faris Shalayel2 1Al-Yarmouk College, Khartoum, 2National College for Medical and Technical Studies, Khartoum, Sudan 1. Introduction It is just to remember that “Pathophysiology” refers to the study of alterations in normal body function (physiology and biochemistry) which result in disease. E.g. changes in the normal thyroid hormone level causes either hyper or hypothyroidism. Changes in insulin level as a decrease in its blood level or a decrease in its action will cause hyperglycemia and finally diabetes mellitus. Scientists agreed that gestational diabetes mellitus (GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy. From our experience most women with GDM in the developing countries are not aware of the symptoms (i.e., the disease will be symptomless). While some of the women will have few symptoms and their GDM is most commonly diagnosed by routine blood examinations during pregnancy which detect inappropriate high level of glucose in their blood samples. GDM should be confirmed by doing fasting blood glucose and oral glucose tolerance test (OGTT), according to the WHO diagnostic criteria for diabetes. A decrease in insulin sensitivity (i.e. an increase in insulin resistance) is normally seen during pregnancy to spare the glucose for the fetus. This is attributed to the effects of placental hormones. In a few women the physiological changes during pregnancy result in impaired glucose tolerance which might develop diabetes mellitus (GDM). The prevalence of GDM ranges from 1% to 14% of all pregnancies depending on the population studied and the diagnostic tests used. -
Orphan G Protein-Coupled Receptors and Obesity
European Journal of Pharmacology 500 (2004) 243–253 www.elsevier.com/locate/ejphar Review Orphan G protein-coupled receptors and obesity Yan-Ling Xua, Valerie R. Jacksonb, Olivier Civellia,b,* aDepartment of Pharmacology, University of California Irvine, 101 Theory Dr., Suite 200, Irvine, CA 92612, USA bDepartment of Developmental and Cell Biology, University of California Irvine, 101 Theory Dr, Irvine, CA 92612, USA Accepted 1 July 2004 Available online 19 August 2004 Abstract The use of orphan G protein-coupled receptors (GPCRs) as targets to identify new transmitters has led over the last decade to the discovery of 12 novel neuropeptide families. Each one of these new neuropeptides has opened its own field of research, has brought new insights in distinct pathophysiological conditions and has offered new potentials for therapeutic applications. Interestingly, several of these novel peptides have seen their roles converge on one physiological response: the regulation of food intake and energy expenditure. In this manuscript, we discuss four deorphanized GPCR systems, the ghrelin, orexins/hypocretins, melanin-concentrating hormone (MCH) and neuropeptide B/neuropeptide W (NPB/NPW) systems, and review our knowledge of their role in the regulation of energy balance and of their potential use in therapies directed at feeding disorders. D 2004 Elsevier B.V. All rights reserved. Keywords: Feeding; Ghrelin; Orexin/hypocretin; Melanin-concentrating hormone; Neuropeptide B; Neuropeptide W Contents 1. Introduction............................................................ 244 2. Searching for the natural ligands of orphan GPCRs ....................................... 244 2.1. Reverse pharmacology .................................................. 244 2.2. Orphan receptor strategy ................................................. 244 3. Orphan receptors and obesity................................................... 245 3.1. The ghrelin system .................................................... 245 3.2. -
FOH 8 Metabolic Syndrome.Indd
Metabolic Syndrome 3 out of 5 criteria for diagnosis Pathological levels? Fasting glucose Waist circumference Blood pressure Triglycerides HDL-Cholesterol Our Routine Laboratory Tests Intact Proinsulin Adiponectin OxLDL / MDA Adduct CRP (high sensitive) IDK® TNFa Haptoglobin Vitamin B1 Tests for your Research Adenosine Resistin ADMA Xpress Relaxin ADMA (Mouse/Rat) OPG AOPP total sRANKL Carbonylated Proteins IDK® TNFa RBP/RBP4 IDK® Zonulin US: all products: Research Use Only. Not for use in diagnostic procedures. www.immundiagnostik.com Metabolic Syndrome Adiponectin total (human) (ELISA) (K 6250) Determination of the adiponectin level as a prevention for Type-2-Diabetes Retinol-binding protein RBP/RBP4 (ELISA) (K 6110) Influence on glucose homeostasis and the development of insulin sensitivity / resistance Convenient marker for Type-2-Diabetes and for cardiovascular risk Resistin (ELISA) (on request) Link between adipositas and insulin resistance? ID Vit® Vitamin B1 (colorimetric test) (KIF001) Diabetes patients exhibit a low Vitamin B1 plasma level Also available: Other Vitamin B ID Vit® tests IDK® Zonulin (ELISA) (K 5601 ) Understanding the dynamic interaction between zonulin and diabetes. High zonulin levels are associated with Type-1-Diabetes Vasoconstriction / Vasodilatation Relaxin (ELISA) (K 9210) Endogenous antagonist of endothelin. Vasodilatator, increases microcirculation Urotensin II ( RUO) (on request) Most powerful vasoconstrictor known Oxidative Stress / Arteriosclerosis ADMA Xpress (Asymmetric -
A Summary About Relaxin and Its Reproductive Function
Endocrinology & Metabolism International Journal Review Article Open Access A summary about relaxin and its reproductive function Abstract Volume 4 Issue 5 - 2017 Relaxin is a pleiotropic hormone included in the insulin-like-growth factor family (IGF) Alana Aragon-Herrera,1 Sandra Feijoo- that is produced in a variety of reproductive tissues including corpus luteum, uterus, testis, Bandin,1,2 Diego Rodriguez-Penas,1 Manuel prostate and others. Relaxin facilitates parturition, participates in uterine contractility, 2,3 2,3 promotes angiogenesis, plays a role in spermatogenesis or promotes spermatozoa motility Portoles, Esther Rosello-Lleti, Miguel 2,3 1,2 and acrosome reaction, among others physiological functions. In this review, we will focus Rivera, Jose Ramon Gonzalez-Juanatey, on the principal roles of relaxin in female and male reproduction. Francisca Lago1,2 1Cellular and Molecular Cardiology Research Unit and Keywords: relaxin, reproduction, parturition, pregnancy, spermatogenesis, male Department of Cardiology of Institute of Biomedical Research reproduction, angiogenesis and University Clinical Hospital, Spain 2Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares, Spain 3La Fe University Hospital, Spain Correspondence: Alana Aragón-Herrera, Unidad de Investigación en Cardiología Celular y Molecular (7), Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Planta -2, Edificio de Consultas Externas, Hospital Clínico Universitario, Travesía Choupana s/n, 15706 Santiago de Compostela, Spain, -
Fetal Growth Signals
Arch Dis Child: first published as 10.1136/adc.64.1_Spec_No.53 on 1 January 1989. Downloaded from Archives of Disease in Childhood, 1989, 64, 53-57 Current topic Fetal growth signals R D G MILNER AND D J HILL Department of Paediatrics, Children's Hospital, Sheffield Human fetal growth is not uniform. Tissue patterns growth factor fi like peptide is found in the vegetal and organ primordia are established during embryo- pole ectoderm of the early Xenopus embryo and is genesis, then from the end of the first trimester and transcribed by a maternally derived gene designated throughout the second the fetus undergoes massive Vgl. An ectodermal cell line, XTC, from the meta- hyperplasia. In the third trimester further organ morphosing tadpole releases a transforming growth modelling and functional maturation occur in pre- factor I8 like peptide in vitro.5 In the 11-18 day fetal paration for extrauterine life. Each aspect ofdevelop- mouse transforming growth factor 3 can be detected ment requires orchestrated intercellular signalling at in bone and connective tissue, particularly that two levels. The release of peptide growth factors derived from neural crest such as palate, larynx, and the modulation of an extracellular matrix are facial mesenchyme, and teeth.6 Staining was most paracrine actions that occur within cell populations intense at sites of tissue morphogenesis affecting and between adjacent germ layers. In contrast, mesodermal and epithelial interaction such as hair endocrine hormones may stimulate growth non- follicles, teeth, and secondary palate. copyright. specifically or promote specific maturational events. Recently both fibroblast growth factor and trans- The interactions between paracrinology, endocrino- forming growth factor i have been shown to exert logy, and environmental constraints to growth remarkable effects on embryonal morphology. -
REVIEW ARTICLE Relaxin Family Peptides: Structure–Activity Relationship Studies
British Journal of British Journal of Pharmacology (2017) 174 950–961 950 BJP Pharmacology Themed Section: Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors REVIEW ARTICLE Relaxin family peptides: structure–activity relationship studies Correspondence Mohammed Akhter Hossain, PhD, and Prof Ross A. D. Bathgate, PhD, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia. E-mail: akhter.hossain@florey.edu.au; bathgate@florey.edu.au Received 5 August 2016; Revised 25 November 2016; Accepted 28 November 2016 Nitin A Patil1,2,KJohanRosengren3, Frances Separovic2 ,JohnDWade1,2, Ross A D Bathgate1,3 and Mohammed Akhter Hossain1,2 1The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia, 2School of Chemistry, University of Melbourne, Parkville, VIC, Australia, and 3Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, Australia The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family peptide receptors, RXFP1–4. As these peptides play a vital role physiologically and in various diseases, they are of considerable importance for drug discovery and development. Detailed structure–activity relationship (SAR) studies towards understanding the role of important residues in each of these peptides have been reported over the years and utilized for the design of antag- onists and minimized agonist variants. This review summarizes the current knowledge of the SAR of human relaxin 2 (H2 relaxin), human relaxin 3 (H3 relaxin), human insulin-like peptide 3 (INSL3) and human insulin-like peptide 5 (INSL5). LINKED ARTICLES This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. -
Relaxin and the Paraventricular Nucleus of the Hypothalamus
Relaxin and the Paraventricular Nucleus of the Hypothalamus by Megan Susan McGlashan A Thesis Presented to The University of Guelph In partial fulfillment of requirements for the degree of Master of Science in Biomedical sciences Guelph, Ontario, Canada © Megan S. McGlashan, August, 2013 ABSTRACT RELAXIN AND THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS Megan Susan McGlashan Advisor: University of Guelph, 2013 Professor A. J. S. Summerlee The hormone relaxin regulates the release of the magnocellular hormones, oxytocin and vasopressin, from the central nervous system. Studies have yet to determine whether relaxin regulates magnocellular hormone release through the circumventricular organs alone, or whether relaxin can act on the brain regions containing the magnocellular neurons as well. The paraventricular nucleus of the hypothalamus was isolated from other brain regions and maintained in vitro, in order evaluate the effects of the relaxin and relaxin-3 on the somatodendritic release of oxytocin and vasopressin. At 50 nM concentrations, relaxin induced oxytocin release, while relaxin-3 inhibited oxytocin release. Neither relaxin nor relaxin-3 had an effect on the vasopressin release, however the RXFP3 specific agonist, R3/I5, induced vasopressin release. The effect of the relaxin peptides on the electrical activity of neurons in the paraventricular nucleus was also evaluated. Relaxin depolarized magnocellular neurons while relaxin-3 hyperpolarized the neurons. Relaxin and relaxin-3 appear to have differential effects on the magnocellular neurons of the paraventricular nucleus. iii ACKNOWLEDGEMENTS When we first enter graduate school, we are very much children in the ways of research. As the saying goes, it takes a village to raise a child, so it was for my master’s degree. -
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, -
Regulation of Glucokinase As Lslets Adapt to Pregnancy
Matschinsky FM, Magnuson MA (eds): Glucokinase and Glycemic Disease: From Basics to Novel Therapeutics. Front Diabetes. Basel, Karger, 2004, vol 16, pp 222-239 Regulationof Glucokinaseas lsletsAdapt to Pregnancy RobertL. Sorenson,Anthony J. Weinhaus,T. Clark Brelje Department of Genetics Cell Biology and Development, University of Minnesota Medical School, Minneapolis,Minn., USA Pregnancyis an occasionin the life history of the B-cell where there is an increasedneed for insulinthat'occurs over a relativelyshort period of time. This amountsto daysin rodentsand monthsin humans.The needfor enhanced islet function emergesas a consequenceof an increasein peripheralinsulin resistanceat the sametime as the placenta,a major targetorgan for insulin, develops.To accommodatethis increasein insulin demand,the islet must undergochanges that lead to increasedinsulin secretionunder normal glucose conditions. The primary short-termregulation of insulin secretionis achievedby ele- vating the glucoseconcentration. However, if this were the primary adaptive mechanismsduring pregnancy,there would be a need for persistenthyper- glycemia- a conditiondeleterious to the developingembryo, fetus and mother. Thus, in the face of this increaseddemand for insulin, islets must undergo structuraland functional changes.The outcomeof this long term upregulation of isletsmust be enhancedinsulin secretion at normalglucose levels. Failure of this long-termadaptive process can lead to gestationaldiabetes. Evidence for functional changes in islets during pregnancy first appearedin the 1960sshortly after the developmentof a sensitiveradioimm- unoassayfor insulin. Spellacyand coworkers[1 3] reportedthat there was a progressiveincrease in both fasting and glucose-stimulatedinsulin secretion throughoutthe courseof pregnancy.These and subsequentstudies led to the charucterizationof pregnancyas a condition of elevatedserum insulin levels, slightly lower blood glucose levels and peripheralinsulin resistance(see reviews[4, 5]). -
Hormonal Regulation of Fetal Growth
Inrntuterine Growth Reianlaliim, edited by Jacques Senterre. Nestle Nutrition Workshop Scries, Vol. 18. Nestec Ltd.. Vevey/Raven Press. Ltd., New York © 1989. Hormonal Regulation of Fetal Growth Jean Girard Centre de Recherche sur la Nutrition (CNRS), 92190 Meudon-Bellevue, France The regulation of fetal growth is complex and still very poorly understood. It in- volves genetic factors, maternal nutrition and cardiovascular adaptations, placental growth and function, and to a lesser extent fetal factors, including fetal hormones. The influence of genetic, maternal, and placental factors on fetal growth has been reviewed recently (1) and will not be discussed. The purpose of this chapter is to analyze the specific role of endocrine factors in the determination of fetal growth, assuming that the nutritional supply to the placenta and to the fetus remains un- altered. The major endocrine factors involved in postnatal growth are: (a) growth hor- mone (GH) via the secretion of somatomedin; (b) thyroid hormones; (c) cortisol; and (d) sex steroids at puberty (2,3). Insulin is considered to have a merely permis- sive role in postnatal growth (2,3). In recent years, a body of evidence has accumu- lated to indicate that the fetus may be less dependent on pituitary and thyroid hormones for growth than the older organism, and more dependent on insulin and tissue growth factors. Studies on the endocrine regulation of fetal growth have in- volved several major approaches: ablation of fetal endocrine glands; examination of newborns with congenital endocrine deficiencies; treatment of fetuses with hor- mones; measurement of plasma hormone concentrations and tissue receptor levels during normal or abnormal growth; and in vitro studies of hormone effects on fetal tissues.