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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.

Immunology of Clinical and Experimental Diabetes

'I. Experimental Diabetes.- 1. Structure and Function of Insulin.- I. Introduction.- II. Three-Dimensional Structure of Insulin in Crystals.- A. Crystal Forms.- B. Insulin in Clinical Preparations.- C. The Structure of Insulin in Crystals.- III. Insulin Structure in Solution.- A. Bovine and Porcine Insulin.- B. Species Variants.- IV. Insulin Biosynthesis.- V. Insulin in Storage Granules.- VI. Evolutionary Differences in Insulin.- A. Evolution of the Insulin Cell.- B. Variations in Insulin Sequences.- C. Proinsulin, Insulinlike Growth Factor, and Relaxin.- VII. Insulin Receptor Binding and Potency.- A. The Active Site of Insulin.- B. The Active Site of Insulinlike Growth Factor.- C. The Negative Cooperative Site of Insulin.- VIII. Immunogenicity and Three-Dimensional Structure.- A. Antigenicity to Clinical Preparations.- B. Antigenicity and the Conformation of Insulin.- References.- 2. Genetic Control of the Immune Response to Insulin in Man and Experimental Animals.- I. Genetic Control of the Immune Response to Insulin in Guinea Pigs and Mice.- A. Guinea Pigs.- B. Mice.- II. Immunity to Insulin in Humans.- References.- 3. Virus and Experimental Diabetes.- I. Introduction.- II. Experimental Model with Polyendocrine Disease and Autoimmunity.- III. Experimental Models with Immunopathological Reactions to the B Cells of Islets of Langerhans.- A. Streptozotocin with Activated Type C Virus.- B. EMC Virus.- IV. Critical Evaluation.- References.- 4. Animal Models of Human Type I Diabetes.- I. Applicability of Animal Models of Diabetes.- II. Experimentally Induced Diabetes.- A. Chemical Agents.- B. Virus-Induced Diabetes.- III. Spontaneous Diabetes.- A. Chinese Hamster (Cricetulus Griseus).- B. South African Hamsters (Mystromys Alb.).- C. Nonobese Diabetic Mouse.- D. Guinea Pig.- E. New Zealand White Rabbit.- F. Canine Models.- G. Nonhuman Primates.- H. BB Rat.- References.- 5. Immune Function in Obese, Diabetic, Hyperinsulinemic C57BL/KsJ-db+/db+ and C57BL/6J-ob/ob Mice.- I. The C57BL/KsJ-db+/db+ Mouse.- A. Introduction.- B. Alterations in Immunological Function.- II. The C57BL/6J-ob/ob Mouse.- A. Introduction.- B. Alterations in Immunological Function.- III. Summary and Conclusions.- References.- 6. The Influence of Sex Hormones on Immunological Processes in the Induction of Diabetes.- I. Introduction.- II. Sex Hormones and Immune Response.- III. Sex Hormones and Diabetes.- IV. Discussion and Conclusion.- References.- 7. Transplantation of Pancreas and Islets.- I. Rationale and Statement of the Problems.- II. Experimental Transplantation.- A. Pancreas with Exocrine Drainage Established.- B. Segmental Pancreas Transplantation without Provision for Exocrine Drainage.- C. Metabolic Efficiency of Pancreatic Transplantation.- D. Immunological Aspects of Pancreatic Allotransplantation.- E. Preservation of the Intact Pancreas.- III. Experimental Transplantation of Free Grafts of Islet Tissue.- A. Source and Preparation.- B. Results in Rodents.- C. Results in Large Animals.- D. Islet Transplantation in Natural Models of Diabetes.- E. Immunological Aspects of Islet Allo- and Xenotransplantation.- F. Preservation of Islet Tissue.- IV. Effect of Transplantation on Secondary Lesions in Experimental Diabetes.- V. Clinical Transplantation: A Brief Summary.- VI. Summary and Prospects.- References.- II. Clinical Diabetes.- 8. Antibodies to Insulin and Insulin Receptors: Mechanisms of Insulin Resistance.- I. Introduction.- II. Insulin Resistance due to Antiinsulin Antibodies.- A. Structure and Antigenicity of Insulin.- B. Genetics of the Immune Response.- C. Clinical Measurements of Insulin Antibodies.- D. Insulin Resistance due to Antiinsulin Antibodies.- E. Therapy.- III. The Insulin Receptor.- A. Clinical Syndrome Associated with Antibodies to the Insulin Receptor.- B. Methods for Detecting Antibodies to the Insulin Receptor.- C. Effects of Antirecep