Advances in Drug Research [Vol 27] (Antidiabetic Agents) - H. Ammon, et. al., (AP, 1996) WW

255 Pages·1996·11.25 MB·English

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ADVANCES IN DRUG RESEARCH

VOLUME 27

Edited by

BERNARD TESTA
School of Pharmacy, University of Lausanne
Lausanne, Switzerland
and
URS A. MEYER
Institute of Pharmacology
University of Basel, Basel
Switzerland

ANTIDIABETIC AGENTS

Recent Advances in their Molecular
and Clinical Pharmacology

by

H. P. T. Ammon, H. U. H~iring,
M. Kellerer, H. Laube, L. Mosthaf,
E. J. Verspohl and M. A. Wahl

ACADEMIC PRESS

Harcourt Brace & Company, Publishers

LONDON
SAN DIEGO NEW YORK BOSTON
SYDNEY TOKYO
TORONTO

ACADEMIC PRESS LIMITED
24-28 Oval Road
LONDON NWl 7DX

U.S. Edition Published by
ACADEMIC PRESS INC.
San Diego, CA 92101

This book is printed on acid-free paper

Copyright � 9 1996 ACADEMIC PRESS LIMITED

All rights reserved
No part of this book may be reproduced or transmitted in any form or by any
means, electronic or mechanical including photocopying, recording or any
information storage and retrieval system without permission in writing from the
publisher

A catalogue record for this book is available from the British Library

ISBN 0-12-013327-X

Typeset by Keyset Composition, Colchester, Essex
Printed in Great Britain by Hartnolls Ltd, Bodmin, Cornwall

CONTENTS

CONTRIBUTORS
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ix

FOREWORD
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xi

PREFACE
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xiii

ABBREVIATIONS
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XV

Introduction
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Regulation of Glucose Homoeostasis

1 Introduction
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2 Effect of Insulin Deficiency .
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3 Regulation of Glucose Homoeostatis in Type-I Diabetes
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4 Regulation of Glucose Homoeostasis in Type-II Diabetes
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Clinical Aspects of Diabetes Mellitus

1 Type-I Diabetes Mellitus
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2 Type-II Diabetes Mellitus .
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Mechanisms of Insulin Action

1 Insulin Actions
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2 Insulin Receptor .
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3 Signal Transduction .
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4 Effector Systems of Insulin Signals: A Limited Selection . . . .
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Therapeutic Use of Insulin

1" Chemistry
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2 Preparations
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3 Application of Insulins .
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4 Pharmacokinetics .
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5 Toxic Effects
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6 Side Effects
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7' Clinical Studies of Insulin-replacement Therapy
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vi
CONTENTS

The Secretory Machinery of Insulin Release

1 Introduction
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2 Route by which Initiators and Modulators Reach the B-Cell
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3 Initiation of Insulin Secretion .
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4 Modulation of Insulin Secretion via Adenylate Cyclase and
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5 Concept of Initiation and Modulation of Insulin Secretion
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Compounds Acting on Insulin Secretion: Sulphonylureas

1 Chemical Structure
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2 Actions .
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3 Pharmacokinetics
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4 Toxic Effects
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5 Side Effects
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6 Interaction with Other Drugs .
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7 Clinical Studies
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Compounds Acting on Glucose Uptake: Biguanides

1 Chemistry
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2 Pharmacology .
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3 Pharmacokinetics .
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4 Toxic Effects
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5 Side Effects
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6 Interactions with Other Drugs
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7 Clinical Studies
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Compounds Acting on Glucose Absorption

1 Guar .
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2 Acarbose
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Aldose Reductase Inhibitors as New Antidiabetic Drugs

1 Chemistry
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2 Functions of Aldose Reductase
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3 Action of Aldose Reductase Inhibitors .
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4 Pharmacokinetics .
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5 Pathological Changes in the Pharmacokinetics .
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6 Toxic and Side Effects
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CONTENTS
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7 Interaction with Other Drugs .
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8 Clinical Trials .
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177

Conclusions
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179

References
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181

SUBJECT INDEX .
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215

CUMULATIVE INDEX OF AUTHORS
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229

CUMULATIVE INDEX OF TITLES
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CONTRIBUTORS

H. P. T. AMMON, Lehrstuhl Pharmakologie, Pharmazeutisches Institut,
Universitiit Tiibingen, Auf der Morgenstelle 8, D-72076 Tiibingen, Ger-
many
H. U. HA, RIN6, Institut fiir Diabetes-Forschung, Krankenhaus Schwabing,
KOlner Platz 1, D-80804 Miinchen, Germany
M. KELLERER, Institut fiir Diabetes-Forschung, Krankenhaus Schwabing,
KOlner Platz 1, D-80804 Miinchen, Germany
H. LAUBE, Medizinische Klinik der Universitiit Gieflen, Rodthohl 6, D-35392
Gieflen, Germany
L. MOSTHAF, Institut for Diabetes-Forschung, Krankenhaus Schwabing,
KOlner Platz 1, D-80804 Miinchen, Germany
E. J. VERSPOHL, Institut fiir Pharmazeutische Chemie, Hittorfstrasse 58-62,
D-48149 Miinster, Germany
M. A. WAHL, Lehrstuhl Pharmakologie, Pharmazeutisches Institut, Univer-
sitiit Tiibingen, Auf der Morgenstelle 8, D-72076 Tiibingen, Germany