In the words of Disraeli, "To be conscious that you are ignorant of the facts is a great step to knowledge. " For most of us, the conscious awareness of relative ignorance is an uncomfortable aspect of daily life. New data appear in such inexorable profusion that the necessity for continuous retooling has joined death and taxes as an inescapable component of our destinies. Perhaps it is this "consciousness of ignorance" that accounts for the success of the preceding volumes of this new series. The Year in Metabolism and The Year in Endocrinology series were introduced with the avowed intention of "providing an efficient and enjoyable bridge between those who are creating new knowledge at the bedside and the professional consciousness of those for whom such knowledge is ultimately intended. " That objective seems particularly appropriate at a time when the award of the 1977 Nobel Prize in Medicine or Physiology to Guillemin, Schally, and Yalow has served to emphasize the epoch-making advances that have characterized the recent course of endocrinology and me bolism. For the 1977 volume of The Year in Metabolism, the previous formula has been preserved. The same internationally recognized authorities again have contributed commentaries about the progress in their areas of expertise. They have been joined by Drs. Jack W. Coburn, David L. Hartenbower, and Charles R. Kleeman, who have provided a new section on Divalent Ion Metabolism.

We are especially grateful to Dr. Philip Corfman and his colleagues of the Population and Reproduction Grants Branch of NICHD for making this Conference possible. The format of this volume follows in general the order in which the papers were presented during the Conference. The Conference was divided into four sessions, each of which was presided over by a capable and distinguished scientist. Each of these chairmen, Drs. T. H. Hamilton, G. A. Puca, R. L. Vande Wiele and H. G. Williams-Ashman provided valuable discussion and for their services we are most appreciative. The Editors are indebted to Mr. Robert Colligan for his help in organizing and in redacting the manuscripts. A special commen dation is also extended to Ms. Mary Jane Fowler who cheerfully and efficiently typed this entire volume. Finally, we express thanks to the individual participants of the Conference for their cooperation and prompt submission of the manuscripts and to the Plenum Press for ensuring the rapid publica tion of this volume. Anthony R. Means, Ph.D. Bert W. O'Malley, M. D."

The tenth meeting of the International Foundation for Biochemical Endocrinology was held in Geilo, Norway near the end of September, 1982. The subject matter of the conference and the monograph was on "Regulation of Target Cell Respon- siveness." The local organizing committee was Asbj rn Aakvaag and Vidar Hansson. The scientific sessions covered a wide range of hormone action and cell response, including: peptide hormones and target cell response, regulation of insulin responsiveness, intracellular modulation of peptide hormone response, gonado- tropins and target cell responses, hypothalamic hormone- effects and regulation, steroid receptors and cellular control, hormones and growth regulation, and hormones and gene regulation. The chairpersons for the sessions were L. Birnbauer - A. Aakvaag, S. Taylor - R. S. Horn, F. Labrie - F. Rommerts, A. R. Means - K. W. McKerns, P. F. Hall - V. Hansson K. Griffiths - K. M. Gautvik, E. J. Peck, Jr. - E. Haug, F. S. French - W. T. Schrader, and E. M. Ritzen - B. Jegou. In addition to the scientific sessions in Geilo we were all delighted to sample some of the cultural and artistic attractions of Oslo, and to travel by train from Oslo via Geilo to Bergen. The scenery and hospitality were magnifi- cant.

Most of us spend at least two-thirds of our lives either sitting or standing. It is somewhat surprising, therefore, to find not a single book devoted to disorders caused by derangements of the normal physiological adjustments to changes in posture. In fact, until very recently, medical students have not even been advised to measure the blood pressure and heart rate in the upright posture as part of the routine physical examination. Although Bradbury and Eggleston first described orthostatic hypotension as a consequence of autonomic insufficiency in 1925, interest in orthostatic disorders has been slow to develop in the subsequent years. It is well known that the change from recumbency to the standing posture stimulates neurological, endocrine, and cardiovascular adjustments that ensure maintenance of a normal circulation despite the effects of gravitational forces. The mechanisms of these physiological responses to orthostasis have been stud ied by many investigators. Some of the defects to which antigravitational com pensatory mechanisms are subject, such as postural hypotension resulting from autonomic failure, have been studied intensively and have become part of the general knowledge of most medical practitioners. Other orthostatic disorders such as various other postural abnormalities of blood pressure control, and orthostatic edema-have received far less attention and have been unable to compete with the more dramatic and life-threatening ailments of humankind for a place in our standard medical texts. These disorders often give rise to distressing symptoms and may lead to severe impairment of health.

The tenth meeting of the International Foundation for Biochemical Endocrinology was held in Geilo, Norway near the end of September, 1982. The subject matter of the conference and the monograph was on "Regulation of Target Cell Respon- siveness." The local organizing committee was Asbjjllrn Aakvaag and Vidar Hansson. The scientific sessions covered a wide range of hormone action and cell response, including: peptide hormones and target cell response, regulation of insulin responsiveness, intracellular modulation of peptide hormone response, gonado- tropins and target cell responses, hypothalamic hormone- effects and regulation, steroid receptors and cellular control, hormones and growth regulation, and hormones and gene regulation. The chairpersons for the sessions were L. Birnbauer -A. Aakvaag, S. Taylor- R. S. Horn, F. Labrie- F. Rommerts, A. R. Means - K. W. McKerns, P. F. Hall - V. Hansson K. Griffiths - K. M. Gautvik, E. J. Peck, Jr. -E. Haug, F. S. French- W. T. Schrader, and E. M. Ritzen- B. Jegou. In addition to the scientific sessions in Geilo we were all delighted to sample some of the cultural and artistic attractions of Oslo, and to travel by train from Oslo via Geilo to Bergen. The scenery and hospitality were magnifi- cant.

It is unclear, and really no longer relevant, whether the information explosion that we now contend with has been fostered by the growth of specialization and subspecialization in medicine, or vice versa. What is clear is that the two are mutually supportive and constitute what would be in endocrine parlance a short-loop positive feedback system. As a result, for most areas of medicine, even the subspecialist in that area has a problem in maintaining currency, the more general specialist has substan tial difficulty in doing so, and the generalist is tempted to abandon the effort altogether. Nevertheless, for all, both the internal pressures of conscience and self-esteem and the external pressures generated by peer review, recertifi cation, and subspecialty boards create the need for continuous self-educa tion. We are, therefore, in an era in which the means of dissemination of new information deserves as much creative attention as does its acquisition.

The Fifth Annual Washington Spring Symposium on Health Sciences attracted over 400 scientists from 20 countries. It was held at the Lisner Auditorium of the George Washington University in Washington. D.C. The theme of the meeting was neural and endocrine peptides and receptors. The meeting emphasized basic and clinical research on neural and endocrine peptides and receptors. The six plenary sessions emphasized pituitary peptides, releasing factors, brain peptides, growth factors, peripheral peptides, and clinical applications. The chapters in this volume are derived from each of these six scientific sessions plus the poster and special sessions. The Abraham White Distinguished Scientist A ward was presented to Dr. Julius Axelrod for his numerous contributions to the field of neurochemistry. He presented the keynote address, which was entitled "The Regulation of the Release of ACTH." Dr. Axelrod discussed numerous factors, such as the peptides CRF, VIP, and somatostatin, that regulate hormone secretion from pituitary cells. The Distinguished Public Service Award was presented to Senator Lowell Weicker, Jr., in recognition of his leadership and outstanding achievements in the United States Senate and for his legislative support for biomedical research and education. In the symposium banquet address, Senator Weicker stressed the need for continued federal support of biomedical science research.

The areas of experimental and clinical psychopharmacology have continued to grow in terms of the numbers of studies appearing in the literature as well as the activity generated by other disciplines that has influenced the output of behavioral pharmacology research. Psychoactive drugs have been considered for their comparative effects upon selected behaviors or for their effect upon diverse behaviors. Behavioral circum stances certainly influence not only the metabolism and action of psycho tropic drugs behaviorally, but also the disposition of these agents and/ or their metabolites in regions of the central nervous system. There can hardly be a psychopharmacology without a neuropharmacology, and the latter would seem to depend upon a neurochemistry. There would appear to be variables that exert potent influences upon the disposition and action of psychotropic drugs, that also relate quite directly to their effects upon behavior; these include drug interactions, nutritional status, environmental effects such as temperature, photic and tactile stimulation, and stress, and the basal status upon which such drug treatment is superimposed. In this volume of Current Developments in Psychopharmacology, which will be the last to appear in this format, we have sought to focus upon a series of current topical reviews that highlight representative areas of experimental and clinical research activity in psychopharmacology. In the first chapter, Dr. Lagerspetz reviews a frequently neglected aspect of psychopharmacological research-the actions of psychoactive agents upon the nervous system and behavior of non-mammalian species."

Diabetes. Its Medical and Cultural History covers the history of scientific inquiry into this affliction from antiquity to the discovery of insulin (1921) with concurrent consideration of the history of the patient and the cultural historical background. The reprints of medical historical studies discuss general relationships as well as specific details and exceptional research achievements of the past. Included in the bibliography of primary sources are the most important historical contributions in diabetic research and diabetic therapy with the author's name and information on the place of publication. The bibliography of secondary literature consolidates international studies from the past century to the present on the history of the theory of diabetes and therapeutic approaches. Illustrations and literary texts document cultural historical relationships. In index of persons and items facilitates use of this work which is intended to provide a stimulus for the physician, medical historian, medical student, general historian as well as diabetics themselves.

During the past 5 years, impressive progress has been made in understanding the etiopathogenesis of expeiimental and clinical diabetes. The rapid progress that has been made in the general field of immunology has made possible new understanding regarding the role of the immune system in the pathogenesis of diabetes. The other two areas in which recent progress has been made in the field of diabetes include genetics and the role of infectious agent(s) in the etiopathogenesis of diabetes. Because of these recent developments, a vast amount of data has been accumulated and published in a number of metabolic, endocrine, immunological, and general medicine journals. The purpose of this book is to consolidate all the available information and present it in its current state. In the present volume, I strive to bring together relevant contributions from leaders in the fields of immunopathology, immunobiology, and genetics. The advancing understanding has in several instances reached the point of clinical applica tion. This volume encompasses the entire scope of modem immunology of diabetes mellitus. This volume has been divided into two major parts, Experimental Diabetes and Clinical Diabetes. In the Experimental part are included chapters dealing with the structure and functions of insulin and the immune response to insulin. Spontaneous and experimentally induced models of type I diabetes mellitus are presented. The role of virus(es) in the etiology of experimental diabetes and the influence of sex on experi mental diabetes are discussed. The transplantation of pancreas and islets is reviewed in detail."

The central nervous system controls vital functions by ef?ciently coordinating peripheral and central cascades of signals and networks in an orchestrated manner. Historically, the brain was considered to be insulin independent. These earlier views have been challenged by ?ndings demonstrating that insulin exerts multiple actions in the brain, regulating vital biological processes such as life span, neuronal survival, cognition, reproduction, feeding behavior, energy balance, and glucose and fat metabolism, and that inef?cient central action of insulin contributes to the development of severe pathologies (Banks et al. 2000; Gerozissis 2003, 2004, 2008; Lustman and Clouse 2005; Okamoto et al. 2001; Park 2002; Perrin et al. 2004; Pocai et al. 2005; Reger et al. 2008; Schwartz and Porte, 2005; Schubert et al. 2004; van der Heide et al. 2005; Woods et al. 1979; Wrighten et al. 2008). Insulin and speci?c insulin receptors are widely distributed in the networks of the central nervous system related mainly to feeding or cognition (Baskin et al. 1983; Bruning et al. 2000; Gerozissis 2003, 2008; Havrankova et al. 1978a, b; Schechter et al. 1996; Schulingkamp et al. 2000; Schwartz et al. 1992; Zhao et al. 2004). Insulin receptors located in the synapses of neurons and in astrocytes are present in high concentrations in the cerebral cortex, olfactory bulb, hippocampus, amygdala, cerebellum and hypothalamus (Abbott et al., 1999; Havrankova et al.

I consider it an honor to have been asked to write the Foreword for The Diabetic Pancreas. Although I have been involved in the study of the pancreas since 1921, my interest goes back even further to the time, in 1918, that my father's sister, a nurse who had trained at the Massachusetts General Hospit.al, devel oped diabetes, lost weight, and died in diabetic coma. This sad event made a deep impression on me and was certainly pardy responsible for my choosing to join the Department of Physiology of the University of Toronto to begin a career in research into diabetes. This is not the place to describe in detail the wide-ranging research and study of the diabetic pancreas in which I have engaged in the past 56 years. Suffice it to say that I am familiar enough with the subject area to be able to predict a great future for this book. The editors have undertaken a very ambitious and worthwhile project, and their efforts have been supported and strengthened by contributors who are respected authorities in their fields, thus ensuring a successful presentation of this major work."

Fundamental to survival of living organisms is their ability to react appropri ately to their environment. Cannon (1929) recognized that "back of internal homeostatic mechanisms are powerful motivating agencies-appetites and hunger and thirst." Almost all observed behavior may be viewed as activity required to meet some physical or emotional need. "The higher in the scale of living things, the more numerous, the more perfect, and the more compli cated do these regulatory agencies become." This statement by Fredricq (1885) regarding internal mechanisms is at least as valid for behavior. Adrenal medullary secretion in preparation of "fight or flight" may be con sidered the first described behavioral neuroendocrine response. The conse quences of more prolonged stress on pituitary-adrenal cortical function and the subsequent unfolding of the means by which the brain controls the secre tion of the anterior and posterior pituitary glands led to the birth of neuroen docrinology. During the last decade, neuroendocrinology has taken a remarkable turn. Peptides which were believed at first to be involved solely in control of the pituitary by the hypothalamus were found in other areas of the brain. Other peptides were encountered in brain by their activity in competing for the high affinity binding of drugs to their receptors, and still others, first found in peripheral organs, were discovered also in brain. Perhaps even more amaz ing was the discovery that one or another of these peptides influence almost every aspect of behavior."

It is curious that research in endocrinology has largely ignored the testis until quite recently. There were two impor tant reasons for this neglect; first, methods of study were difficult, and second, sperinatogenesis was considered to be the concern of the urologist or cell biologist but not the endocrinologist. Since it is now almost an ethical imperative that we develop a male contraceptive, and since a host of new techniques can be brought to bear on problems of testis function, research in male reproductive biology has effloresced. In fact, it has become possible to project aseries of workshops on the testis, each dealing with discrete aspects of biochemistry, physiology and pathology. It is fitting that this first Workshop should be on Binding and Activation, since this area is one of the frontiers in endocrinol ogy. At our present rate of progress it is probable that each of the succeeding workshops will likewise bring together leaders in a rapidly developing area. The National Institute of Child Health and Human Development has the major Federal respon sibility in reproductive biology, and has therefore agreed to sponsor this and succeeding workshops. On behalf of the Institute and for those members of the Committee who have organized this meeting, I welcome you. I am quite sure that this first Workshop on the Testis will initiate aseries of important contributions to scientific thought in male reproduc tive biology. Mortimer B. Lipsett, M. D."

Paget's disease is an old disease historically, but a new disease therapeutic ally. Human remains unearthed in Lancashire, England, dating from ap proximately 900 AD, show clear evidence of the aftliction. However, it was not until the 1800s that physicians rediscovered the condition, and a little more than 100 years ago that Sir James Paget published a perceptive and accurate description of the disease from the clinical and pathologic points of view. He felt the disease represented an inflammatory condition of the skeleton and hence named it osteitis deformans. The condition again lapsed into anonymity for several decades afterwards, and therapeutic approaches did not evolve until after World War II when several groups, located mainly in the Boston area, began using a variety of agents, includ ing corticosteroids for treatment of this condition. These early attempts at therapy were unsuccessful and the condition remained essentially untreat able until the development of the calcitonins and the bisphosphonates in the 1970s. In 1978, the Paget's Disease Foundation, a private nonprofit volun tary health agency, was founded to assist individuals aftlicted by Paget's disease of bone, to provide education regarding this condition to the medical community, and to encourage research efforts to better under stand and treat the condition. An international conference was organized under the aegis of the Paget's Disease Foundation and was held in New York City in October, 1989, ten years after the founding of the Paget's Disease Foundation."

Tumours of the prostate are the commonest types of neoplasm in the male. Whilst the benign form is virtually a universal condition in the ageing male, malignant tumours rank amongst the top causes of cancer death. Despite the fact that the involvement of the testis in the growth of the prostate has been recognised for almost two centuries, it was not until the early 1940s that Charles Huggins' studies on the effect of orchidectomy and oestrogen therapy on prostatic cancer initiated endocrine manipulation in the management of this malignancy. During the 1960s progress in the understanding of the mechanism of hormone action, achieved through advances in molecular biology and the recognition of certain aspects of hormonal control in relation to the genome, introduced a new dimension for approaching endocrine manipulation of prostatic tumours. By the end of that decade a new scientific discipline devoted to prostate research had been born, which brought together investigators in the fields of molecular biology, biochemistry, endocrinology, immunology, urology and pathology to search for the cause and to explore methods for advancing the management of abnormal prostatic growth. Since then a wealth of scientific data has accumulated on the prostate in which endocrinology has manifested itself as the cardinal aspect to which most of the findings can be related.

This volume is devoted to the chemistry, immunology, molecular biology, and physiology of the human chorionic gonadotropin, heG. For this glycoprotein molecule the course from discovery to chemical deciphering covered about fifty years. It was in 1928 that Ascheim and Zondek reported that urine from pregnant women contains something that stimulates the ovaries of mice or rats. This provided the basis for the famous A-Z test for pregnancy and for the "rabbit test" modification introduced by Friedman. As researchers sought to find more sensitive responses to heG, they used a wide variety of species including the South African aquatic toad, Xenopus Zaevis, the terrestrial toad of South America, Bufo arinarus, and the African weaver finch, EupZeetes afra. The weaver finch feather reaction was particularly noteworthy, for it disclosed a non-gonadal response to heG/LH. In retrospect, this may have been an important evolutionary clue to the realization that the designation of the hormone as a "gonadotropin" may have been only partially descriptive of the molecule's physiological function--a concept that is gaining attention, as the papers in this 1980 volume divulge.

This volume contains the papers presented at the Inter- national Symposium on "Cirrhosis, Hepatic Encephalopathy and Ammonium Toxicity", held in Valencia, Spain, November 27-29, 1989. Hepatic cirrhosis as well as other liver failures usual- ly lead to hepatic encephalopathy which is an important cause of death in occidental countries. However the molecular bases of the pathogenesis of hepatic encephalopathy remain unclear and several hypotheses have been proposed. Hyperammonemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy. Therefore, a part of the book is devoted to the effects of hyperammonemia on cerebral function, ammonia and amino acid metabolism, brain microtobules, astrocytes and synaptic trans- mission and their possible role in the pathogenesis of hepatic encephalopathy. Carnitine has a remarkable protective effect against acute ammonium intoxication. Thus some results regarding this effect are also presented, as well as the clinical use of car- nitine. The alterations of the metabolism of ammonia and of seda- tives in liver diseases and their clinical implications are also discussed. The possible role of altered GABA-ergic neurotransmission on the pathogenesis of hepatic encephalopathy has received considerable attention recently. Results of these studies and those on benzodiazepine receptor ligands are presented as well as those on the hypothesis of the role of altered synaptic plasma membrane on the pathogenesis of hepatic encephalopathy.

Diabetes is one of the oldest diseases known to mankind. It was first mentioned in the Ebers Payrus (Egypt 1500 BC) and 'honey urine' was noted by Sushrutha in India in 400 BC. By the first century of the Christian era the disease was well known, both in Roman writings and in Chinese and Japanese writings. The word 'diabetes' was first coined by the Greeks. It means a passing-through of water. They described it as a 'melting of flesh into water', meaning urine. Then in 1674 Doctor Willis discovered by heating, tasting and evaporating urine that a sweet sticky substance was in it, which, of course, was sugar. Rut sugar was not known in England in those days and honey was the only real sweet tasting substance. The Latin word 'mel' which means honey was used and the disease came to be known as diabetes mellitus - that is, the passing of honeyed urine. This is still the full name of the disease.

The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap plied in neuronal tissue to the neurohypophysis.

Can the art of predictive medicine anticipate the development of diabetes? And if so, what can be done about it? How early is early enough to intervene effectively? With what therapeutic modality? Why? Big babies are not an infrequent occurrence in mothers with normal carbohydrate metabolism for another 10, 20, or even 30 years. The abnor- mality present during pregnancy is now accepted as what is inherited with the diabetic predisposition, or what can be recognized as the diabetic susceptibility. It occurs before hyperglycemia, during the phase of dy- namic resistance to diabetes, during the prediabetic period. Prediabetes means before diabetes, and was applied for the first time by Mara~on in Spain, to signify the stage before hyperglycemia. Foglia in Argentina used the term in 1944 for his pancreatectomized rats. We pub- lished the first paper on humans in 1951 (Camerini-Davalos, R.A., Landabure, P., and Serantes, N., Rev Med Cordoba 39: 187).

Despite a new title, Contemporary Metabolism, Volume 1 is actually the third volume in a continuing series and succeeds The Year in Metabolism 1975- 1976 and The Year in Metabolism 1977. As in the earlier volumes, the same internationally recognized authorities review the noteworthy recent devel opments in their areas of expertise. In many instances they also address aspects that have not been considered previously. In this volume, Dr. J. Edwin Seegmiller again updates progress in understanding disorders of purine and pyrimidine metabolism. However, particular emphasis is placed on the emerging relationships with immune mechanisms. Dr. Charles S. Lieber is joined by Dr. Enrique Baraona in a continuing review of metabolic actions of ethanol. This chapter examines effects of ethanol on protein metabolism and selected features of lipid metabolism-two areas that were not included in the earlier volumes. Dr. DeWitt S. Goodman's review of disorders oflipid and lipoprotein metabo lism builds on his previous chapters, but much additional attention is directed to a critical analysis of recent advances in epidemiology and lipoprotein structures. In collaboration with Dr. Brian L. G. Morgan, Dr. Myron Winick devotes his entire chapter to a detailed review of the impact of nutrition upon brain development-an overview that has now been rendered possible by the burgeoning recent developments in this area."

During the past several decades, much research effort has gone into the elucidation of the role of neuroendocrine systems as secretory and metabolic regulators of cells of a variety of organs and structures, including the testes, ovaries, adrenals, thyroid, pituitary gland, and mammary glands. However, the role of cells comprising such organs and structures in the modulation of neuroendocrine processes has received considerably less is generally less well appreciated. attention and Nonetheless, it is important that we understand the actions on neuroendocrine systems of substances that reach the brain by way of the vasculature, including hormones, cytokines, toxins, amino acids, drugs, and similar agents. In order to analyze the present state of knowledge on this topic, experimental scientists and clinicians, whose shared interests include actions of circulating agents on the brain, met at a satellite symposium of the XXXI International Congress of Physiological Sciences. This symposium, entitled Circulating Regulatory Factors and Neuroendocrine Function, was held in Smolenice Castle, Czechoslovakia, June 26-July 1, 1989, and reviews delivered at this symposium as invited presentations are published in this volume. Presentations given as free communications have been published separately and are available in Endocrinologia Experimentalis 24: 1-273, 1990.

THE DISCOVERY OF INSULIN, C-PEPTIDE AND PROINSULlN, SPECIES DIFFERENCES Crude insulin was extracted and isolated from dog pancreases removed 7-1 Degrees weeks after ligation of the pancreatic duct for the first time in 1921 by Banting and Best. Its lifesaving properties were subsequently documented in pancreatectomized dogs in 1922. Only about six months elapsed from its discovery until systematic collection of calf and ox pancreases and, later, porcine pancreases was established and the blood glucose lowering effect in diabetics using the crude extract from these glands proven. It was not until 1960, however, that the primary structure of all three species of insulin, lO7 human, porcine and bovine, was elucidated . It then became evident that the differences between bovine, porcine and human insulin amounted to at mosl 3 amino acids. These apparently small differences have a significant impact on the physico-chemical characteristics of the three insulins which again affect, e.g., the rate of absorption of insulin lO9 preparations from the subcutaneous tissue and their immunogenicity, i.e.

Diabetes, particularly type 2, has become increasingly more common around the world. Consequently, the effect of diabetes on the brain has achieved enormous public health importance. A surge in pre-clinical and clinical research on topics ranging from management of hyperglycemia in acute stroke to disturbances in insulin signaling in Alzheimer s disease has led to substantial progress in the field. Written by a panel of international experts, Diabetes and the Brain provides in depth reviews on the cerebral complications of diabetes, and offers introductory chapters on current insights on the pathophysiology and clinical management of diabetes, as well as neuropsychological assessment and dementia. This relevant and easily accessible book explains the cerebral complications of diabetes, with an update on diabetes for neurologists, psychiatrists, and mental health providers and researchers in general, and on stroke and dementia for those involved in research and clinical practice in diabetes."