Glucagon III PDF
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Handbook of Experimental Pharmacology Volume 123 Editorial Board G.V.R.Born,London P. Cuatrecasas, Ann Arbor, MI D. Ganten, Berlin H. Herken, Berlin K.L. Melmon, Stanford, CA Springer Berlin Heidelberg New York Barcelona Budapest Hong Kong London Milan Paris Santa Clara Singapore Tokyo Glucagon I I I Contributors J.M. Amatruda, D. Bataille, D. Bennis, H.-P. Bode P.E. Cryer, C.F. Deacon, H.-C. Fehmann, N. Geary B. Goke, R. Goke, J.J. Holst, V. Iwanij, M.M. Johnson T. Kornfelt, P.J. Lefebvre, J.N. Livingston, I. Mollerup M.A. Nauck, P. Oreskov, C. 0rskov, G. Paolisso, C. Pavoine F. Peeker, J. Philippe, A.J. Scheen, J. Skucas, G. Slama B. Thorens, H.V. Tszjttrup, C. Widmann, G.P. Zaloga P. Zirinis Editor Pierre J. Lefebvre Springer Professor PIERRE J. LEFEBVRE, M.D., Ph.D., FRCP Centre Hospitalier Universitaire de Liege Department of Medicine Division of Diabetes, Nutrition, and Metabolic Disorders C.H.U. Sart Tilman B-4000 Liege 1 Belgium With 69 Figures and 7 Tables ISBN -13:978-3-642-64718-5 Library of Congress Cataloging in Publication Data. Main entry under title: Glucagon. (Handbook of experi mental pharmacology: v. 123 Bibliography: p. Includes index. I. Glucagon-Adresses, essays, lectures. I. Lefebvre, Pierre J. II. Series. [DNLM: I. Glucagon. WI HA5IL vol. 66 pt. 1-2IWK 801G5656) QP905:H3 vol. 123 [QP572.G5) 615'ls [612'.34) 83-583 ISBN -13:978-3-642-64718-5 e-ISBN-13 :978-3-642-61150-6 DOl: 10.1007/978-3-642-61150-6 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,recitation, broadcasting, reproduction on microfilm or in any other ways, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1996 Softcover reprint of the hardcover 1st edition 1996 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: Design & Production, Heidelberg Typesetting: Best-set Typesetter Ltd., Hong Kong SPIN: 10497518 27/3136/SPS-5 4 3 2 1 ~Printed on acid-free paper Preface Glucagon III supplements Glucagon I and II, also published in the Handbook of Experimental Pharmacology (vols. 66 I, II), updating the encyclopedic information compiled on glucagon, the hyperglycemic hormone produced by the A-cells in the islets of Langerhans of the pancreas. Since 1983, the year of publication of Glucagon I and II, the increase in our knowledge on glucagon has been immense: the glucagon gene and the glucagon receptor gene have been identified, the biosynthesis of glucagon has been elucidated, and our understanding of the mode of action of the hormone has been revised. The role of glucagon in diabetes is now recognized, and the search for glucagon antagonists is active. Furthermore, glucagon is used not only to treat hypoglycemia but also as a useful agent in emergency medicine, an interesting drug to improve imaging of the gut, and a useful tool to evaluate residual insulin secretion. Recent data also indicate that glucagon might be involved in the regulation of appetite. Another member of the glucagon family, glucagon like peptide 1 or GLP-1, has now been clearly identified. It is recognized as a major "incretin," stimulating the release of insulin in response to food inges tion. GLP-1 appears to have a great future in the management of diabetes while another glucagon-related peptide, oxyntomodulin, seems to playa major role in the control of gastric acid secretion. These various topics are covered in the 19 chapters of the present volume, all of which have been written by recognized world experts. Individuals working on glucagon will find Glucagon III to be an unrivaled source of information, joining volumes I and II as the standard references on this subject. Hospital physicians are likely to be interested in the chapters on the role of glucagon in diabetes, the modes of glucagon adminis tration, the place of glucagon in emergency medicine and in medical imaging, the glucagon test for evaluating insulin secretion, and glucagonoma and its management. I wish to thank the authors for their comprehensive contributions and - almost all of them - for having sent their chapters on the agreed deadline. This permits us to present a perfectly updated volume. Thanks go also to my secretary, Mrs. E. Vaessen-Petit, who, once again, helped me in the editorial process, to Mrs. D. Walker who has been a most efficient contact with the publisher, and to Mr. W. Shufflebotham, an excellent copy editor. VI Preface Glucagon I and II received an enthusiastic welcome when they were published in 1983. I wish the same fate to the third volume of the trilogy some 13 years later. Liege July 1996 PIERRE J. LEFEBVRE List of Contributors AMATRUDA, 1.M., Bayer Corporation, Pharmaceutical Division, Metabolic Disorders Research, Building B-24, 400 Morgan Lane, West Haven, CT 06516-4175, USA BATAILLE, D., INSERM U376, CHU Arnaud-de-Villeneuve, 34295 Montpellier Cedex OS, France BENNIS, D., Service de Diabetologie, Hotel-Dieu, 1, place du Parvis Notre Dame, 75181 Paris Cedex 04, France BODE, H.-P., Clinical Research Unit for Gastrointestinal Endocrinology, De partment of Internal Medicine, Philipps-University Marburg, Baldinger strasse, 35033 Marburg, Germany CRYER, P.E., Division of Endocrinology, Diabetes and Metabolism, Washing ton University School of Medicine, Campus Box 8127, 660 S. Euclid Avenue, St. Louis, MO 63110, USA DEACON, C.F., Institute of Medical Physiology C, The Panum Instituttet, University of Copenhagen, Blegdamsvej 3,2200 Copenhagen N, Denmark FEHMANN, H.-C., Clinical Research Unit for Gastrointestinal Endocrino logy, Department of Internal Medicine, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany GEARY, N., E.W. Bourne Behavioral Research Laboratory, New York Hospital, Cornell Medical Center, 21 Bloomingdale Road, White Plains, NY 10605, USA GOKE, B., Clinical Research Unit for Gastrointestinal Endocrinology, Depart ment of Internal Medicine, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany GOKE, R., Clinical Research Unit for Gastrointestinal Endocrinology, Depart ment of Internal Medicine, Philipps-University Marburg, Baldingerstrasse, 35033 Marburg, Germany VIII List of Contributors HOLST, J.J., Department of Medical Physiology, The Panum Instituttet, University of Copenhagen, Blegdamsvej 3,2200 Copenhagen N, Denmark IWANIJ, V., Department of Genetics and Cell Biology, University of Minne sota, College of Biological Sciences, 250 Biological Sciences Center, 1445 Gortner Avenue, St. Paul, MN 55108-1095, USA JOHNSON, M.M., Department of Medicine, Pulmonary Critical Care, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1009, USA KORNFELT, T., Novo Nordisk, Hagedornsvej 1, 2820 Gentofte, Denmark LEFEBVRE, P.J., Centre Hospitalier Universitaire de Liege, Department of Medicine, Division of Diabetes, Nutrition and Metabolic Disorders, C.H.U. Sart Tilman (B35), 4000 Liege 1, Belgium LIVINGSTON, J.N., Bayer Corporation, Pharmaceutical Division, Metabolic Disorders Research, Building B-24, 400 Morgan Lane, West Haven, CT 06516-4175, USA MOLLERUP, 1., Novo Nordisk, Hagedornsvej 1,2820 Gentofte, Denmark NAUCK, M.A., Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University, In der Schornau, 44892 Bochum-Langendreer, Germany ORESKOV, P., Novo Nordisk, Novo AIle, 2880 Bagsvaerd, Denmark 0RSKOV, c., Institute of Medical Anatomy, The Panum Instituttet, University of Copenhagen, Blegdamsvej 3,2200 Copenhagen N, Denmark PAOLISSO, G., Department of Geriatric Medicine and Metabolic Diseases, II University of Naples, 80138, Naples, Italy PAVOINE, c., Unite de Recherches INSERM U99, Hopital Henri Mondor, 94010 Creteil, France PECKER, F., Unite de Recherches INSERM U99, Hopital Henri Mondor, 94010 Creteil, France PHILIPPE, J., Department de Medecine, Division d'Endrocrinolgie et Diabetologie, Hopital Cantonal Universitaire, Unite de Diabetologie Clinique, 1211 Geneva 14, Switzerland List of Contributors IX SCHEEN, A.J., Centre Hospitalier Universitaire de Liege, Department of Medi cine, Division of Diabetes, Nutrition and Metabolic Disorders, C.H.U. Sart Tilman (B35), 4000 Liege 1, Belgium SKUCAS, J., Department of Diagnostic Radiology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 648, Rochester, NY 14642- 8648, USA SLAMA, G., Service de Diabetologie, Hotel-Dieu, 1, place du Parvis Notre Dame, 75004 Paris, France THORENS, B., Institute of Pharmacology and Toxicology, University of Lausanne, 27, Rue du Bugnon, 1005 Lausanne, Switzerland Tl/.iTIRUP, H.V., Novo Nordisk, Hagedomsvej 1,2820 Gentofte, Denmark WIDMANN, c., Institute of Pharmacology and Toxicology, University of Lausanne, 27, Rue du Bugnon, 1005 Lausanne, Switzerland ZALOGA, G.P., Section on Critical Care, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1009, USA ZIRINIS, P., Service de Diabetologie, Hotel-Dieu, 1, place du Parvis Notre Dame, 75181 Paris Cedex 04, France Contents CHAPTER 1 The Industrial Production of Glucagon I. MOLLERup, T. KORNFELT, P. ORESKOV, and H.V. TjljTTRUP With 7 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 A. Introduction............................................... 1 B. Production................................................ 1 I. Expression and Fermentation. . . . . . . . . . . . . .. . . . . . . . .. . . . 1 II. Recovery and Purification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1. Recovery.......................................... 1 2. Purification........................................ 2 3. Aggregation....................................... 3 III. Pharmaceutical Preparations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 C. Analysis of Recombinant Human Glucagon. . . . . . . . . . . . . . . . . . . . 3 I. Introduction.......................................... 3 II. Identification......................................... 3 III. Purity............................................... 4 1. Microbiological Impurities. . . . . . . . . . . . . . . . . . . . . . . . . . . 4 2. Water............................................. 5 3. Chemical Impurities... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 IV. Assay................................................ 9 D. Stability................................................... 9 References. . . . .. . .. . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . .. 10 CHAPTER 2 The Glucagon Gene and Its Expression J. PHILIPPE. With 8 Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 A. Introduction............................................... 11 B. Structure.................................................. 12 I. The Glucagon Gene. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 II. Genes Encoding Peptide Hormones of the Glucagon Superfamily. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 14 C. Expression................................................. 17
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