Pancreatic Beta Cell in Health and Disease

474 Pages·2008·5.8 MB·English

by  Marcela Brissova, Alvin C. Powers (auth.), Susumu Seino M.D., D.M. Sci., Graeme I. Bell Ph.D. (eds.)

Susumu Seino, Graeme I. Bell (Eds.)
Pancreatic Beta Cell in Health and Disease
Susumu Seino, Graeme I. Bell
(Eds.)
Pancreatic Beta Cell
in Health and Disease
Susumu Seino, M.D., D.M. Sci.
Professor, Division of Cellular and Molecular Medicine, Department of Physiology and
Cell Biology, Kobe University Graduate School of Medicine
7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan
Graeme I. Bell, Ph.D.
Louis Block Distinguished Service Professor, Medicine and Human Genetics,
The University of Chicago
5841 South Maryland Avenue, Chicago, IL 60637, USA
ISBN978-4-431-75451-0 e-ISBN978-4-431-75452-7
Library of Congress Control Number: 2007939279
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Preface
The beta cells of the pancreatic islets of Langerhans are the only cells in the
body that produce and secrete insulin, a key metabolic hormone, which plays
a central role in the maintenance of glucose homeostasis regulating glucose
uptake in muscle and adipose tissue as well as carbohydrate, fat, and protein
metabolism in these tissues and the liver. Failure of normal beta-cell function
can lead to hyperglycemia (diabetes mellitus) or hypoglycemia. While hypo-
glycemia is a rare and life-threatening condition in which the beta cell secretes
too much insulin, diabetes mellitus is a common disorder that is fast becom-
ing an epidemic. It is a major threat to human health in the 21st century. The
number of diabetic patients worldwide is rapidly increasing and is predicted
to reach 380 million by 2025, according to the International Diabetes Federa-
tion (IDF).
Diabetes mellitus is a heterogeneous disorder with some forms such as
maturity-onset diabetes of the young and permanent neonatal diabetes being
primary genetic disorders of the beta cell. Monogenic forms of diabetes are
an uncommon cause of diabetes representing about 1% of cases. The common
forms of diabetes mellitus, designated type 1 and type 2, are multifactorial in
origin with both genetic and environmental factors contributing to their
development. Type 1 diabetes is caused by autoimmune destruction of beta
cells leading to an absolute defi ciency of insulin and fatal hyperglycemia and
ketoacidosis if not treated. Type 2 diabetes is a disorder of relative defi ciency
of insulin resulting when the beta-cell mass is not able to expand and thereby
secrete more insulin in response to an increasing demand such as occurs in
obese individuals. Whatever the form of diabetes, the beta cell plays a central
role in the disease process.
The purpose of this book is to provide a comprehensive up-to-date review
of the beta cell in health and disease. The chapters address the architecture
and pathology of normal and diabetic pancreatic islets; regulation of beta-cell
proliferation and death; the potential of stem cells and extra-pancreatic
V
VI Preface
tissues as beta-cell replacement therapies; insulin biosynthesis from tran-
scription to processing; regulation of insulin secretion including metabolic
control, ion channels, gap junctions, cyclic AMP, incretins and exocytosis;
development of novel imaging techniques to visualize the exocytosis of insulin
granules; and genetic disorders of the beta cell.
We hope this book inspires students and young basic and clinical investiga-
tors to become actively involved in diabetes research and the search for new
approaches for preventing and treating diabetes. In addition, we hope it will
provide encouragement to others in the fi eld. Although we have made a great
deal of progress in understanding the relationship between the beta cell and
health and disease, much remains to be done.
We gratefully acknowledge the contribution to this book by each of the
authors. We thank the editorial staff of Springer Japan who patiently assisted
us throughout the project. Without their effort, this book would not have
been possible.
Editors
Susumu Seino, M.D., D.M. Sci. Graeme I. Bell, Ph.D.
Division of Cellular and Molecular Medicine Departments of Medicine and
Department of Physiology and Cell Biology Human Genetics
Kobe University Graduate School of Medicine The University of Chicago
Kobe, Japan Chicago, IL, USA
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . XI
I: Pancreatic Beta Cell and Insulin Biosynthesis
1. Architecture of Pancreatic Islets
M. Brissova and A.C. Powers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
2. Transcriptional Regulation of Insulin Gene Expression
I. Artner and R. Stein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
3. The Biosynthesis of Insulin
D.F. Steiner . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
II: Cell Signaling and Insulin Secretion
4. Metabolic Regulation of Insulin Secretion
B.E. Corkey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
5. Mechanisms of Beta-Cell Death in Diabetes
M.Y. Donath and J.A. Ehses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
6. Ion Channels and Insulin Secretion
D.A. Jacobson and L.H. Philipson . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
7. Gap Junctions and Insulin Secretion
P. Klee, S. Bavamian, A. Charollais, D. Caille, J. Cancela,
M. Peyrou, and P. Meda . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
8. Protein Kinase A-Independent Mechanism of cAMP in
Insulin Secretion
S. Seino, T. Miki, and T. Shibasaki . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
VII
VIII Contents
9. Regulation of Insulin Granule Exocytosis
E. Renström and P. Rorsman . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
10. Mechanism of Insulin Exocytosis Analyzed by
Imaging Techniques
S. Nagamatsu and M. Ohara-Imaizumi . . . . . . . . . . . . . . . . . . . . . . . 177
11. Two-Photon Excitation Imaging of Insulin Exocytosis
N. Takahashi and H. Kasai . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
III: Pancreatic Development and Beta-Cell Formation
12. Regulation of Beta-Cell Growth and Death
C.J. Rhodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
13. Beta-Cell Replication
S.J. Salpeter and Y. Dor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
14. Stem Cells as a Cure for Diabetes
T. Otonkoski, M. Banerjee, and K. Lundin . . . . . . . . . . . . . . . . . . . . 265
15. Use of Extra-Pancreatic Tissues for Cell Replacement Therapy
for Diabetes
I. Meivar-Levy and S. Ferber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
IV: Incretins and Beta-Cell Function
16. Molecular Biology of Gluco-Incretin Function
S. Klinger and B. Thorens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
17. Incretins and Regulation of Insulin Secretion
M.A. Nauck and J.J. Meier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
V: Pancreatic Beta Cell and Disease
18. Pancreatic Islet Pathology in Type 2 Diabetes
A. Clark . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
19. Genetic Disorders of the Pancreatic Beta Cell and Diabetes
(Permanent Neonatal Diabetes and Maturity-Onset Diabetes
of the Young)
E.L. Edghill and A.T. Hattersley . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
20. ATP-Sensitive Potassium Channels in Health and Disease
P. Proks and F.M. Ashcroft . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Contents IX
21. Glucokinase in Glucose Homeostasis, Diabetes Mellitus,
Hypoglycemia, and as Drug Receptor
F.M. Matschinsky . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
Contributors
Artner, Isabella (p. 13)
Department of Molecular Physiology and Biophysics, Vanderbilt University
Medical Center, 723 Light Hall, Nashville, TN 37232, USA
Ashcroft, Frances M. (p. 431)
Oxford Centre for Gene Function, Department of Physiology, University of
Oxford, Parks Road, Oxford OX13PT, UK
Banerjee, Meenal (p. 265)
Hospital for Children and Adolescents and the Biomedicum Stem Cell
Center, Biomedicum Helsinki, P.O. Box 63, Haartmaninkatu 8, FI-00014
University of Helsinki, Helsinki, Finland
Bavamian, Sabine (p. 111)
Department of Cell Physiology and Metabolism, University of Geneva,
Medical School, 1 rue Michel Servet, 1211 Genève 4, Switzerland
Brissova, Marcela (p. 3)
Division of Diabetes, Endocrinology, and Metabolism, Department of
Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
Caille, Dorothée (p. 111)
Department of Cell Physiology and Metabolism, University of Geneva,
Medical School, 1 rue Michel Servet, 1211 Genève 4, Switzerland
Cancela, José (p. 111)
Department of Cell Physiology and Metabolism, University of Geneva,
Medical School, 1 rue Michel Servet, 1211 Genève 4, Switzerland
XI
XII Contributors
Charollais, Anne (p. 111)
Department of Cell Physiology and Metabolism, University of Geneva,
Medical School, 1 rue Michel Servet, 1211 Genève 4, Switzerland
Clark, Anne (p. 381)
Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology
and Metabolism, Churchill Hospital, Oxford OX37LJ, UK
Corkey, Barbara E. (p. 53)
Obesity Research Center, Department of Medicine, Boston University
School of Medicine, Boston, MA 02118, USA
Donath, Marc Y. (p. 75)
Clinic of Endocrinology and Diabetes, University Hospital Zurich, CH-8091
Zurich, Switzerland
Dor, Yuval (p. 245)
Department of Cellular Biochemistry and Human Genetics, The Hebrew
University–Hadassah Medical School, Jerusalem 91120, Israel
Edghill, Emma L. (p. 399)
Institute of Biomedical and Clinical Science, Peninsula Medical School,
Barrack Road, Exeter, Devon EX25AX, UK
Ehses, Jan A. (p. 75)
Clinic of Endocrinology and Diabetes, University Hospital Zurich, CH-8091
Zurich, Switzerland
Ferber, Sarah (p. 285)
Endocrine Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel
Department of Human Genetics and Molecular Medicine, Sackler School of
Medicine, Tel-Aviv University, Tel-Aviv, Israel
Hattersley, Andrew T. (p. 399)
Institute of Biomedical and Clinical Science, Peninsula Medical School,
Barrack Road, Exeter, Devon EX25AX, UK
Jacobson, David A. (p. 91)
Department of Medicine, The University of Chicago, 5841 S. Maryland Ave.,
MC1027, Chicago, IL 60637, USA