Pancreatic Beta Cell in Health and Disease.pdf

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

ISBN 978-4-431-75451-0

e-ISBN 978-4-431-75452-7

Library of Congress Control Number: 2007939279

This work is subject to copyright. All rights are reserved, whether the whole or part of the material

is concerned, speciﬁ cally the rights of translation, reprinting, reuse of illustrations, recitation, broad-

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that such names are exempt from the relevant protective laws and regulations and therefore free for

general use.

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tion thereof contained in this book. In every individual case the respective user must check its accu-

racy by consulting other pharmaceutical literature.

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Printed in Japan

Typesetting: SNP Best-set Typesetter Ltd., Hong Kong

Printing and binding: Shinano Co. Ltd., Japan

Printed on acid-free paper

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

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