As far as we are aware, this is the first attempt to cover the com parative physiology of the pancreatic islets in a monograph. The topics discussed would probably have sufficed to fill about half a dozen monographs, a matter that becomes obvious from a look at the Contents. Hence, we have tried to present the ma terial more in the form of a digest, to emphasize evolutionary perspectives, to point out critical issues, and to identify challenging topics for future research. This approach required an arbitrary reduction of the num ber of references, and we therefore join the chorus of recent authors who beg their colleagues for understanding if some of their publications do not appear in the bibliography. Keeping up with the current literature was like fighting one of those monsters that grow a couple of new heads for each one that is cut off. Nevertheless, we hope that we have covered most of the key publications up to the autumn of 1986. We gratefully acknowledge the advice of many colleagues, and in particular the invaluable criticisms of Robert L. Hazelwood and Erika Plisetskaya. Special thanks are due to the series editor, Donald S. Farner, for his patience and guidance, both of which were fresh proof of his legendary diplomatic skills. Finally, we wish to thank Dr. D. Czeschlik and his staff at the Springer Verlag for their patience and support. Philadelphia, PA AUGUST EpPLE Greenville, NC JACK E. BRINN September 1987 v Contents Chapter 1. Introduction .......................... .

The Evolution of Pancreatic Islets covers the proceedings of the 1975 symposium on The Evolution of Pancreatic Islets, held at Leningrad under the auspices of the Academy of Sciences in Leningrad, U.S.S.R. This symposium brings together numerous studies on the structure, chemistry, and function of the pancreatic islets of animals ranging from the mollusc to man. This book is composed of three parts encompassing twenty seven chapters. The first part deals with the problems related to the production of insulin from its precursor pro-insulin and the ontogeny of the pancreatic islets from the embryonic endoderm. The second part discusses the phylogenetic aspects of the structure of pancreatic islets. This part also looks into the evolutionary morphology and classification of pancreatic acinar-islet cells. The third part describes the biological and chemical aspects of pancreatic hormones of vertebrates.

Pancreatic islets make up the endocrine pancreas and they contain the only source of insulin in the body, beta cells. Hence, access to high quality preparations of pancreatic islets is fundamental for in vitro studies and to test pre-clinical applications in animal models in vivo. Access to healthy human islets is also crucial to improve transplantation procedures for diabetes. Given the susceptibility of pancreatic islets to the enzymatic digestion and mechanical stress required to obtain them, the isolation of islets is often considered as the delicate “work of a craftsman”. This book, which is aimed at beginners and experts alike, is a survey of the current state-of–the-art in this field and it centres on the challenges, pitfalls and peculiarities of pancreatic islet isolation in the different species used in pre-clinical and clinical applications. It explores the similarities and differences between human islets and those from other relevant species (rodents, pigs and non-human primates), and how these influence islet isolation. The ultimate goal of this book is to improve the outcome of islet isolation and transplantation in pre-clinical and clinical applications.

This comprehensive volume discusses in vitro laboratory development of insulin-producing cells. It encompasses multiple aspects of islet biology—from embryonic development and stem cell differentiation to clinical studies in islet transplantation, regulation of islet beta-cell regeneration, pancreatic progenitors, mathematical modelling of islet development, epigenetic regulation, and much more. The chapter authors represent leading laboratories from around the world who contribute their international perspectives and global expertise. Collectively, they provide the reader with a concise yet detailed knowledge of processes and current developments in islet regenerative biology. Pancreatic Islet Biology, part of the Stem Cell Biology and Regenerative Medicine series, is essential reading for researchers and clinicians in stem cells or endocrinology, especially those focusing on diabetes.

Aaron I. Vinik, M.D., Ph.D. I IEastem Virginia Medical School The Diabetes Institutes Norfolk, Virginia 23510 This symposium, held in June 1991, was a gathering of international scientists to exchange their views on current concepts of cell growth and differentiation. Each scientist was asked to present a topic of their research related to cell growth and regeneration and to participate in a round table conference elaborating on current knowledge and sharing their experiences. By furthering this promising area of endeavor, a means of understanding ontogeny of cell development and of providing insights into tumor biology would prevail. Of prime importance was the anticipation that new information from a better understanding of the normal evolution of the pancreatic islet would generate alternative approaches to curing diabetes. This forward serves as a short introduction to the concept of pancreatic islet regeneration and the models currently in use to study the process. DEVELOPMENTAL ORIGIN OF ISLETS DURING EMRYOGENESIS The developing pancreas appears as a protrusion from the dorsal surface of the l embryonic gut. The different islet cell types appear sequentially during development in vivo. It therefore seems reasonable to propose that coordinated growth is dependent upon specificity of growth factors.