The Endocrine Pancreas and Juvenile Diabetes PDF
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THE ENDOCRINE PANCREAS AND JUVENILE DIABETES ADV ANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY Editorial Board: NATHAN BACK, State Univer8ity of New Yark ot Buffalo N. R. DI LUZIO, Tulane Unit>er8ity School of Medicine EPHRAIM KATCHALSKI-KATZIR, The Weizmann IR8titute of Science DAVID KRITCHEVSKY, Wi8tar In8titute ABEL LAJTHA, New Yark State Ruearch IR8titute for Neurochemi8try and Drug Addiction RODOLFO PAOLETTI, Univerrity of Milan Recent Volumes in this Series Volume 117 STEROID HORMONE RECEPTOR SYSTEMS Edited by Wendell W. Leavitt and James H. Clark Volume 118 CELL SUBSTRATES: Their Use in the Production of Vaccines and Other Biologicals Edited by John C. Petricciani, Hope E. Hopps, and Paul J. Chapple Volume 119 TREATMENT OF EARLY DIABETES Edited by Rafael A. Camerini-Davalos and Bernard Hanover Volume 120A KININS - II: Biochemistry, Pathophysiology, and Clinical Aspects Edited by Setsuro Fujii, Hiroshi Morlya, and Tomoji Suzuki Volume 120B KIN INS - II: Systemic Proteases and Cellular Function Edited by Setsuro Fujii, Hiroshi Moriya, and Tomoji Suzuki Volume 121A MACROPHAGES AND LYMPHOCYTES: Nature, .'unctions, and Interaction, Part A Edited by Mario R. Escobar and Herman Friedman Volume 121B MACROPHAGES AND LYMPHOCYTES: Nature, Functions, and Interaction, Part B Edited by Mario R. Escobar and Herman Friedman Volume 122A PURINE METABOLISM IN MAN - III: Clinical and Theoretical Aspects Edited by Aurelio Rapado, C. H. M. M. de Bruyn, and R. W. E. Watts Volume 122B PURINE METABOLISM IN MAN -III: Biochemical, Immunological, and Cancer Research Edited by Aurelio Rapado, C. H. M. M. de Bruyn, and R. W. E. Watts Volume 123 GABA - Biochemistry and CNS Functions Edited by Paul Mandel and Francis V. DeFeudis Volume 124 THE ENDOCRINE PANCREAS AND JUVENILE DIABETES Edited by David M. Klachko, Ralph R. Anderson, Thomas W. Burns, and Harold V. Werner THE ENDOCRINE PANCREAS AND JUVENILE DIABETES Edited by David M. Klachko Ralph R. Anderson Thomas W. Burns and v. Harold Werner University of Missouri· Columbia Columbia, Missouri PLENUM PRESS • NEW YORK AND LONDON Library of Congress Cataloging in Publication Data Midwest Conference on Endocrinology and Metabolism, 13th, University of Missouri, Columbia, 1977. The endocrine pancreas and juvenile diabetes. (Advances in experimental medicine and biology; v. 124) "Proceedings of the Thirteenth Midwest Conference on Endocrinology and Metabolism, held at the University of Missouri, Columbia, Missouri, September 28-30, 1977 and spon sored by the University of Missouri - Columbia, College of Agriculture ... ret al.]" Includes bibliographical references and index. 1. Diabetes - Congresses. 2. Pancreas - Secretions - Congresses. 3. Diabetes in chil dren - Congresses. 4. Diabetic angiopathies - Congresses. I. Klachko, David M. II. University of Missouri - Columbia, College of Agriculture. III. Title. IV. Series. RC660.M531977 616.4'62 79-21998 ISBN-13:978-1-4684-8510-3 e-ISBN-13 :978-1-4684-8508-0 DOl: 10.1007/978-1-4684-8508-0 Proceedings of the Thirteenth Midwest Conference on Endocrinology and Metabolism, held at the University of Missouri, Columbia, Missouri, September 28-30,1977 and sponsored by: University of Missouri - Columbia College of Agriculture Dalton Research Center Department of Biochemistry Department of Child Health Department of Family & Community Medicine Department of Medicine Department of Pharmacology Department of Physiology Department of Radiology Department of Surgery Department of Veterinary Anatomy & Physiology Department of Veterinary Medicine & Surgery Department of Veterinary Pathology Division of Biological Sciences Extension Division Graduate School School of Medicine Sinclair Research Farm University Assembly Lecture Committee Veterinary Medicine Diagnostic Laboratory Eli Lilly and Company Mead Johnson Research Center Ross Laboratories Upjohn Company Wyeth Laboratories © 1979 Plenum Press, New York Softcover reprint of the hardcover 1s t edition 1979 A Division of Plenum Publishing Corporation 227 West 17th Street, New York, N.Y. 10011 All rights 'reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Conference Chairmen RALPH R. ANDERSON, Ph.D., Associate Professor of Dairy Husbandry, UMC DA VID M. KLACHKO, M.D., Associate Professor of Medicine, UMC Planning Committee JOHN D. DAVID, Ph.D., Assistant Professor of Biological Sciences, UMC C. W. FOLEY, Ph.D., Professor of Veterinary Anatomy-Physiology, UMC LEONARD R. FORTE, Ph.D., Associate Professor of Pharmacology, UMC JOHN M. FRANZ, Ph.D., Associate Professor of Biocnemistry, UMC JAMES A. GREEN, Ph.D., rrofessor of Anatomy, UMC LAURENCE W. HEDLUND, Ph.D., Assistant Professor of Dairy Husbandry, UMC MURRA Y HEIMBERG, M.D., Ph.D., Professor of Pharmacology and Medicine, UMC J. ALAN JOHNSON, Ph.D., Assistant Professor of Physiology, UMC CALVIN W. WOODRUFF, Professor of Child Health, UMC WARREN L. ZAHLER, Ph.D., Assistant Professor of Biochemistry, UMC Speakers ROBERT S. BAR, M.D., Assistant Professor of Medicine, Division of Endocrinology and Metabolism, University of Iowa College of Medicine, Iowa City, Iowa BURlS R. BOSHELL, M.D., Ruth Lawson Hanson Professor of Medicine; Medical Director, Diabetes Research and Education Hospital, University of Alabama School of Medicine, Birmingham, Alabama MICHAEL BROWNLEE, M.D., Chief Fellow, Joslin Clinic, Boston, Massachusetts REX S. CLEMENTS, JR., M.D., Associate Professor of Medicine; Director, Clinical Research Center and Metabolic Research Laboratories, University of Alabama, Birmingham, Alabama JOHN E. GERICH, M.D., Associate Professor of Medicine and Physiology; Director of Diabetes and Metabolism Research Laboratory, Mayo Medical School, Rochester, Minnesota RACHMIEL LEVINE, M.D., Executive Medical Director, City of Hope Medical Center, Duarte, California CHARLES R. PARK, M.D., Professor and Chairman, Department of Physiology, Vanderbilt Uni versity School of Medicine, Nashville, Tennessee ARTHUR H. RUBENSTEIN, M.D., Professor and Associate Chairman, Department of Medicine, University of Chicago, Chicago, Illinois MARK A. SPERLING, M.D., Associate Professor of Pediatrics; Chief, Pediatric Endocrinology and Metabolism, U.C.L.A. School of Medicine, Harbor General Hospital, Torrance, California MICHAEL W. STEFFES, M.D., Ph.D., Associate Professor, Department of Laboratory Medicine and Pathology; Medical Director of Clinical Chemistry Laboratory, University of Minnesota Medical School, Minneapolis, Minnesota JOSEPH R. WILLIAMSON, M.D., Professor of Pathology, Washington University School of Med icine, St. Louis, Missouri Moderators THOMAS W. BURNS, M.D., Professor of Medicine and Director, Division of Endocrinology and Metabolism, UMC RICHARD A. GUTHRIE, M.D., Professor and Chairman, Department of Pediatrics, University of Kansas School of Medicine, Wichita, KaD8Il8 ROBERT C. HARDIN, M.D., Professor of Medicine, University of Iowa, Iowa City, Iowa MURRAY HEIMBERG, M.D., Ph.D., Professor and Chairman, Department of Pharmacology, UMC ROBERT L. JACKSON, M.D., Professor of Child Health, UMC HAROLD V. WERNER, Assistant Professor of Medicine, UMC Discussants BREITENBACH, R.P., Division of Biological Sciences, University of Missouri-Columbia BURNS, T. W., Deparbnent of Medicine, University of Missouri-Columbia DAVIS, J. W.,·Department of Biochemistry, Saint Louis University, Saint Louis, Missouri FRANZ, J. M., Department of Biochemistry, University of Missouri-Columbia GUTHRIE, R., Department of Pediatrics, University of Kansas School of Medicine, Wichita, Kansas HAmACH, H., Deparbnent of Radiology, University of Missouri-Columbia HEIMBERG, M., Department of Pharmacology, University of Missouri-Columbia IVEY, K. J., Department of Medicine, University of Missouri-Columbia JACKSON, R. L., Department of Child Health, University of Missouri-Columbia KILO, C., West County Internal Medicine Inc., Saint Louis, Missouri KLACHKO, D. M., Department of Medicine, University of Missouri-Columbia PETERSON, C. M., Department of Medical Biochemistry, The Rockefeller University, New York, New York SANNY, C. G., Department of Biochemistry, College of Osteopathic Medicine and Surgery, Des Moines, Iowa SHEAR, D. B., Department of Biochemistry, University of Missouri-Columbia TOWNSEND, J. F., Department of Pathology, University of Missouri-Columbia VORBECK, M. L., Deparbnent of Pathology, University of Missouri-Columbia WEINSTEIN, I., Department of Pharmacology, University of Missouri-Columbia WERNER, H. V., Department of Medicine, University of Missouri-Colurnbia Preface Dr. Robert L. Jackson, Professor of Child Health at the Uni versity of Missouri-Columbia, decided to retire from clinical practice in 1977 and the Department of Child Health planned a con ference in his honor. The Thirteenth Annual MidweSt Conference on Endocrinology and Metabolism also was in the planning stages and scheduled for two days in the fall. It seemed appropriate to com bine the two into an expanded three-day conference. In view of Dr. Jackson's international reputation in the study and care of children with diabetes mellitus, the conference topic was not dif ficult to find. Experts in this field were delighted to be asked to speak at a conference in Dr. Jackson's honor. We selected a number of excellent speakers to survey the physiology and pathophy siology of pancreatic hormones and their effects in diabetes mel litus, to discuss current knowledge of the microvascular complica tions of the disease, and to put it all into the proper historical perspective of where we have been and where we are going. We think the conference achieved its objective to pay meaningful trib ute to a distinguished member of the scientific community. As with any conference, the conversion of the presentations and discussions to the printed page is a long and arduous process. Many manuscripts were completed well after the conference and references often are more recent than the date of the conference. We wish to express our appreciation to all participants in the conference, to the planning committee, to Mrs. Linda Bennett who typed the copy, to Plenum Press for their assistance and, espe cially, to the sponsors without whom the conference could not have taken place. Ralph R. Anderson Thomas W. Burns David M. Klachko Harold V. Werner vii Robert L. Jackson, M.D. ROBERT LAWRENCE JACKSON Robert Jackson is a native of Michigan and was born in the town of Clare in the central part of the lower peninsula where he attended the public schools. He received the Bachelor of Science degree from Notre Dame University in 1930. Subsequently, he studied at the University of Michigan and was awarded the M.D. de gree. From 1934 to 1937 he was first a rotating intern and then a resident in Pediatrics at the University of Iowa Hospitals, in cluding an exchange residency at the University of Rochester. In the years 1937 to 1954 he remained at the University of Iowa in advancing ranks from Instructor to Professor of Pediatrics. In 1954 he accepted the Chair of Pediatrics at the University of Mis souri-Columbia in which capacity he served until 1973. Since then he has remained active as Professor of Pediatrics. These are but milestones which tell us little about the per son whose journey they mark. He is, and was always, a talented physician, teacher, and research scientist whose energy was spent in making better the lives of children, both sick and well. The interesting questions are: What led him to these endeavors? What did he accomplish? Why did he devote himself to these tasks? The last question, "Why," cannot be answered with certainty because individuals rarely understand themselves so completely and observers never do. Probably what one does in life is a product of opportunity and personality. As will be recounted, Dr. Jackson had an early introduction to biological research and this, judging subsequent events, caught his interest. An even temperament which has enabled him to succeed arises in part, at least, from certain facets of his character of which four come to mind. First, he has a deep religious faith which is a natural part of his everyday life. Second, he is truly a "family man." He and Mrs. Jackson have enjoyed many years together and have raised a family which is a constant source of pleasure and support. ix x ROBERT L. JACKSON Third, he has but one approach to all people. He is a superb clinical scientist and a demanding teacher, but with students, pa tients, patients' parents, and colleagues, the only interpersonal relationship he understands is friendship. A warm regard for him as a person persists in patients and students for years after their initial contact. The fourth characteristic is a true love for children --his own, his patient, or, for that matter, any child. This is the solid base for all his work and is, perhaps, as close as one can come to "why." How he proceeded into his life work is a bit easier to ascer tain. As an undergraduate at Notre Dame he majored in chemistry and as a senior was a laboratory assistant in organic chemistry. It was then that he did his first research which concerned the chemistry of pyridine. While a medical student at Michigan he worked at a community hospital in Ann Arbor, St. Joseph Mercy Hospital, and became involved in investigation into cystinuria and the pharmacological properties of caffeine. Research became a daily part of life as a house officer and soon after he began to focus on two fields in particular --diabetes and nutrition. In many ways these studies were related, particularly those concern ed with the nutritional needs and the growth and development of diabetic children. Dr. Jackson made important contributions in the field of rheumatic heart disease and the prophylaxis of rheu matic fever and in renal disease. However, the major thrust for 40 years has been the management of the juvenile diabetic. Since the discovery of insulin, the treatment of the child with diabetes has been revolutionized. In the beginning, abso lutely nothing was known about what would happen to a diabetic child whose life was prolonged by insulin. Since then, much has been learned and each step of the way has been illuminated by Dr. Jackson. He was influenced by Dr. Julian Boyd who postulated very early that the goal of treatment should be a return to normal physiology, including normal growth and development. Dr. Jackson played a major role in the establishment of norms of growth of well children and demonstrated that these could and should apply to diabetic children. To this end, he conducted nutritional studies and research into the effects of various types of insulin, their combinations, and timing of their use. With his coworkers he demonstrated fully that the diabetic child could achieve a normal life. Finally, he turned his attention to the question of whether the specific vascular disease of diabetes could be prevented by treatment. This last work has continued to the present day and there is now a widening acceptance of the necessity for careful control of the juvenile diabetic. These would seem to be the out-
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