Molecular Biology And Physiology Of Insulin And Insulin Like Growth Factors

This volume addresses a fundamental puzzle in biology and medicine, namely, how does tissue develop, repair and replace itself. The answer appears to lie in growth factors and their regulation. To thrive and survive we need growth factors and this book concentrates on two factors that are related to growth hormone. Growth hormone does not act directly on all tissues, but mediates many of its actions through the release of insulin-like growth factors from the liver. The growth factors were originally called somatomedins by McConaghey and Sledge (1), who discovered that they mediated growth-like effects of growth hormone. However, the factors were purified on the basis of their insulinomimetic actions on fat and muscle and it is their relationship to the insulin family of pep tides that now gives them their name (2,3) of insulin-like growth factors (IGFs). They mediate the actions of. growth hormone on the proteoglycan synthesis of cartilage and produce mitogenic effects in fibroblast cultures.

An essential element in the development and functional integrity of all organisms is intercellular communication. This is achieved by the secretion of soluble messenger molecules which subsequently interact with receptor-effector pathways in the responsive cells. Hormones are traditionally defined as chemical messengers synthesized by endocrine glands. Unlike hormones produced by endocrine glands, growth factors are hormone-related substances produced by many tissues and play an important role in controlling growth and development. While the exact physiological roles of growth factors have yet to be elucidated, they play important roles in the regulation of cellular proliferation and/or differentiation during ontogenesis, growth and differentiation. During recent years there has been a substantial increase in research related to peptide growth factors, their receptors, and modes of action. With the discovery and characterization of numerous growth factors, it became clear that these growth factors had multiple features in common with classic hormones as well as with oncogenes. Furthermore, there are distinct families of growth factors based either on structural or functional similarities.

During the past decade, the continued interest in insulin-related growth factors has been documented by a plethora of research programs and publications focused on these growth factors. Both molecular and cellular biological techniques have improved and enabled investigators to study the properties of the growth factors in depth. This volume covers the molecular (genetic) aspects of the growth factors, their binding proteins and receptors, as well as those factors affecting their gene transcription and translation. In addition, aspects of the cellular action of these growth factors through their receptors and how this impacts normal cellular function are discussed. The book will provide valuable information for researchers in physiology, biology, endocrinology, and metabolism.

It has been over 40 years since the original report by Salmon and Daughaday demon strating that the ability of GH to stimulate sulfation of cartilage was mediated by a "sulfation factor. " In the ensuing decades, it has become apparent that this "sulfation factor activity" encompasses a complex system ofligands (IGFs), receptors, and carrier proteins that are, in tum, responsible for a wide array of cellular actions. The IGF system has been demonstrated to be critically involved in both intrauterine and postnatal growth, and to have important implications in cancer biology as well, owing to the ability of the IGFs to function in endocrine, paracrine, and autocrine modes and given the wide distri bution of IGFs in virtually every organ system. The contributions to The /GF System reflect the wide span of interest in the IGF system and its implications for normal and abnormal growth and metabolism. The chapters have been divided into four broad sections: I. Molecular biology of the IGF system; II. Bio logical actions of the IGFs; III. IGF physiology; and IV. Clinical aspects of the IGFs. We have made every effort to highlight the major contemporary themes in IGF biology, but as is inevitable in such a fast-moving field, perspectives will continue to change as new information is accumulated.

The past decade has seen an explosion in our understanding of the factors regulating cell proliferation and differentiation. One of the most exciting advances has been the recognition of the pivotal role of the peptide growth factors in these processes. The insulin-like growth factors, discovered in 1958 by Salmon and Daughaday, are now among the best characterized growth factors. This comprehensive work describes the recent advances in knowledge of their receptors and binding proteins together with their purification and cloning. This provides exciting insights into the role of these factors in the physiology of normal growth, embryonic development and areas of pathology such as wound healing and cancer. In this book an international group of contributors reviews the most up-to-date information on all aspects of the insulin-like growth factors, and critically discusses models for IGF action in their own systems. The book is a valuable source of information and ideas for researchers, and an accessible introduction to the subject for students and clinicians.

Traditionally, intercellular communication and the regulation of biological functions of the body have been considered the role of two major and distinct systems: the nervous system and the endocrine system. The classic nervous system transmitted its signal rapidly by using electrical currents, whereas the signals used by the endocrine system were hormones produced by endocrine glands which reached the target tissues via the blood stream. During the past few decades, it has become apparent that these systems of intercellular com munication are not distinct and the signal messenger molecules are not unique to one or the other system. Many classic endocrine hormones are found in and act on nervous tissues and evidence exists for their de novo synthesis by neural related tissues. An exciting development in this area is the possibility that insulin and insulin-like growth factors (IGF) are not only produced by neural tissues but also exert profound physiological and biochemical effects on these tissues. The area of investigation of CNS insulin and IGF has been expanding rapidly and the availability of this book complete with up-to-date reviews on the subject by leaders in the field allows other scientists to utilize the knowledge in planning and adapting the latest ideas for future experiments. In addition, the book provides a collection of up-to-date articles for teachers to be used for the latest instructional material. The first section of the book covers general aspects of insulin receptors and insulin action.

How do hormones and growth factors regulate animal growth in the developing embryo and after injury? What processes at the molecular level determine the growth patterns of different tissues? In this diverse synthesis of recent research, the regulation of growth in response to environmental and genetic stimuli is discussed at the level of the animal, tissues and cells. Contrasts are drawn between regulation in fetal and adult tissues, and in different tissues such as the CNS, bone and muscle. Functional chapters focus on the molecular links between mechanical tension and muscle growth, for example, while other chapters review the roles of specific molecules such as hormones and growth factors. This state of the art review will be of significant interest to graduate students and research scientists in the fields of animal growth, endocrinology and cell biology.

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines. This volume focuses on insulin and IGFs. *Longest running series published by Academic Press *Contributions by leading international authorities