Animal Models in Diabetes: A Primer (Frontiers in Animal Diabetes Research)

Animal Models of Diabetes: A Primer introduces characteristics of the most commonly used animal species with various diabetic syndromes which have been developed and extensively investigated during the last few decades. It includes animal models that are readily available, well described and proven to be of value in the research of both types of diabetes. Extensively referenced, this book will be of value to new and established investigators, graduate students and pharmaceutical scientists working on the development of antidiabetic and preventative modalities in various areas of diabetes and its complications. BOOK COVER......Page 1 HALF-TITLE......Page 2 TITLE......Page 4 COPYRIGHT......Page 5 CONTENTS......Page 6 PREFACE TO THE SERIES......Page 8 PREFACE......Page 9 CONTRIBUTORS......Page 10 The Original BioBreeding Colony......Page 17 Genetic Heterogeneity Among BB Bats from Different Sources......Page 18 DIABETES RESISTANT BB RATS......Page 20 OBTAINING BB RATS......Page 21 Clinical Diabetes in BB Rats......Page 22 Pancreatic Insulitis......Page 23 Thyroiditis......Page 24 HUMORAL IMMUNITY IN THE BB RAT......Page 25 CELLULAR AUTOIMMUNITY IN THE BB RAT: A MATTER OF IMMUNOLOGICAL BALANCE......Page 27 Thymocyte Development in the BB Rat......Page 28 RTEs and T Cell Life Span in BB Rats......Page 29 NK T Cells......Page 30 Phenotype......Page 31 Mechanism by Which Autoreactive Cells are Generated......Page 32 REGULATORY CELLS IN THE BB RAT......Page 33 Nomenclature and Genetics of Rat RT6......Page 34 MODULATION OF DIABETES EXPRESSION IN THE BB RAT......Page 35 Immunomodulation by Cytokines, Cells, Antigens, and other Factors......Page 36 Environmental Manipulation: Diet and Infection......Page 37 Induction of IDDM in Resistant Animals......Page 38 iddm2......Page 39 iddm3......Page 40 THE BB RAT AS A MODEL OF HUMAN AUTOIMMUNE DIABETES......Page 41 REFERENCES......Page 43 Origin of the NOD Mouse......Page 54 MAINTENANCE OF THE NOD MOUSE......Page 56 CHARACTERISTICS OF THE NOD MOUSE......Page 57 ENVIRONMENTAL EFFECT ON INCIDENCE OF DIABETES......Page 58 Congenic Strains......Page 59 MHC gene is necessary, but not sufficient for disease development......Page 64 Multiple susceptibility genes on chromosome 3......Page 65 Origin......Page 67 Genetic backgrounds......Page 68 REFERENCES......Page 69 CURRENT NOMENCLATURE FOR THE MOUSE MUTATIONS......Page 72 Origin of the C57BL/6J (B6) and the C57BLKS/J (BKS) strains......Page 73 Influence of B6 and BKS background modifiers on the expression of Lepob and Leprdb......Page 74 METABOLIC DEFECTS AND THE SEARCH FOR THE PRIMARY LESIONS......Page 76 IDENTIFICATION OF THE PRIMARY MOLECULAR DEFECTS......Page 77 BEHAVIORAL CHARACTERISTICS OF B6-Lepab AND BKS-Leprdb MICE......Page 79 PHYSIOLOGICAL AND BIOCHEMICAL CHARACTERISTICS IN B6-Lepob MICE......Page 81 PHYSIOLOGIC AND BIOCHEMICAL CHARACTERISTICS OF MICE......Page 85 SECONDARY COMPLICATIONS......Page 88 REPRODUCTIVE CHARACTERISTICS IN B6-Lepob MICE......Page 90 OTHER FEATURES OF BKS-Leprdb AND/OR B6-Lepob MICE......Page 91 SOURCE COLONIES OF Lepob MICE......Page 94 BREEDING SCHEMES FOR EARLY PHENOTYPIC IDENTIFICATION OF THE Leprdb MUTATION......Page 96 HUSBANDRY CONSIDERATIONS......Page 97 EXPERIMENTAL TECHNIQUES......Page 98 CONCLUDING REMARKS......Page 99 REFERENCES......Page 100 INTRODUCTION......Page 111 PHENOTYPIC APPEARANCES......Page 113 PANCREATIC ABNORMALITIES......Page 114 Insulin Secretion......Page 115 Over-Expression of OB-R......Page 116 Ceramide Metabolism......Page 117 Lipids and Lipoproteins......Page 118 Vascular Changes......Page 119 Gastric Mobility......Page 120 PPARr Agonists......Page 121 Other Treatments......Page 122 REFERENCE......Page 123 INTRODUCTION......Page 129 STRAIN DIFFERENCE FOR DIABETOGENIC ACTION OF OBESITY......Page 130 INSULIN RESISTANCE......Page 131 OTHER CHARACTERISTICS RESPONSIBLE FOR NIDDM......Page 134 HISTOLOGICAL CHANGES AND COMPLICATIONS......Page 135 CHROMOSOME MAPPING......Page 136 USEFUL FOR EVALUATION OF ANTIDIABETIC DRUGS......Page 137 REFERENCES......Page 138 SUMMARY......Page 142 HISTORICAL BACKGROUND......Page 143 Blood Pressure and Cardiovascular Characteristics......Page 144 Hyperlipidemia......Page 146 Vascular Disease......Page 147 Leptin......Page 148 Endocrine pancreas......Page 149 Reproductive function......Page 150 Weight cycling......Page 151 High sucrose diet......Page 152 Conclusion......Page 153 REFERENCES......Page 154 ESTABLISHMENT AND UTILIZATION......Page 157 Mechanism of Insulin Resistance......Page 159 NEPHROPATHY......Page 162 CONCLUSION......Page 163 REFERENCES......Page 165 INTRODUCTION......Page 168 METABOLIC CHARACTERISTICS OF NZO MICE......Page 169 INSULIN SECRETION STUDIES......Page 171 Muscle and Fat Insulin Resistance......Page 172 Hepatic Insulin Resistance......Page 174 IMMUNE ABNORMALITIES......Page 176 REFERENCES......Page 177 INTRODUCTION......Page 180 ORIGIN......Page 181 Growth curve of NSY mice......Page 182 Insulin secretion......Page 183 INHERITANCE OF DIABETES......Page 184 SUSCEPTIBILITY LOCI FOR DIABETES MELLITUS......Page 186 A Candidate Gene for Nidd1nsy......Page 187 PRACTICAL INFORMATION......Page 188 REFERENCES......Page 189 ORIGIN AND BREEDING OF THE GK RAT......Page 190 Maintenance and Breeding of the GK Rat; Some Practical Considerations......Page 191 GENETIC CONSIDERATIONS......Page 192 Islet Structure and Composition......Page 193 Pancreatic and Islet Hormone Content......Page 194 Glucose-induced Insulin Secretion......Page 195 Insulin Response to Nonglucose Secretagogues......Page 197 INSULIN SENSITIVITY......Page 198 CONCLUDING REMARKS......Page 199 REFERENCES......Page 200 11. THE OLETF RAT......Page 204 PROCESS OF BREEDING OLETF RATS......Page 205 GENERAL PATHOPHYSIOLOGY......Page 206 RENAL COMPLICATION......Page 207 DISCUSSION......Page 209 RENAL COMPLICATION......Page 210 REFERENCES......Page 213 12 THE JCR: LA-cp RAT: AN ANIMAL MODEL OF OBESITY AND INSULIN RESISTANCE WITH SPONTANEOUS CARDIOVASCULAR DISEASE......Page 215 HISTORICAL BACKGROUND......Page 216 Insulin Resistance and Hyperlipidemia......Page 217 Cardiovascular Disease......Page 219 COMPARISON WITH OTHER OBESE RAT STRAINS......Page 221 MAINTENANCE OF THE STRAIN......Page 222 Animal Handling and Drug Administration......Page 224 Diurnal Cycle......Page 225 Assessment of Insulin and Glucose Metabolism......Page 226 POTENTIAL USES OF THE JCR:LA-cp RAT......Page 227 AVAILABILITY AND SHIPPING......Page 228 REFERENCES......Page 229 NEONATAL STREPTOZOTOCIN MODELS (n-STZ)......Page 232 Insulin Secretion in Response to Glucose and Non-glucose Secretagogues......Page 235 Incompetence of β-cells to Glucose in n-STZ Models: Intracellular Mechanisms......Page 236 Loss of Glucose-induced Insulin Release in n-STZ Models: Is it Reversible?......Page 239 INSULIN ACTION IN n-STZ MODELS......Page 241 n-STZ Diabetic Models and Obesity......Page 244 NEONATAL STREPTOZOTOCIN DIABETES: SPONTANEOUS REMISSION AND β-CELL REGENERATION......Page 245 n-STZ MODELS AND COMPLICATIONS OF LONGSTANDING NIDDM......Page 246 REFERENCES......Page 247 INTRODUCTION......Page 253 ADVANTAGES OF THE GALACTOSEMIC RAT......Page 254 DIETS AND CARE FOR GALACTOSE-FED RATS......Page 256 TISSUE CARBOHYDRATE MEASUREMENTS......Page 257 ELASTASE RETINAL DIGEST PROCEDURES......Page 258 MEASUREMENTS OF CAPILLARY BASEMENT MEMBRANE THICKNESS......Page 263 MORPHOMETRY OF RETINAL VASCULAR WHOLE MOUNTS......Page 264 MECHANISM(S) UNDERLYING DIABETIC COMPLICATIONS......Page 265 DIABETIC RETINOPATHY—PREVENTION STUDIES......Page 266 CLINICAL TRIALS......Page 268 DIABETIC RETINOPATHY—EARLY AND LATE INTERVENTION STUDIES......Page 269 RELATIVE ROLES OF GLYCATION AND OXIDATION......Page 270 NEOVASCULARIZATION/VASCULOGENESIS: POTENTIAL ROLE OF OXYGEN......Page 275 SIGNIFICANCE OF THE GALACTOSEMIC RAT MODEL......Page 276 REFERENCES......Page 277 15. THE RHESUS MONKEY (MACACA MULATTA): A UNIQUE AND VALUABLE MODEL FOR THE STUDY OF SPONTANEOUS DIABETES MELLITUS AND ASSOCIATED CONDITIONS......Page 285 Activity......Page 291 Special Care Considerations......Page 292 Sedation and anesthesia......Page 293 SUPPLIERS AND SOURCES FOR THIS MODEL......Page 294 MOST SUITABLE AREAS OF RESEARCH WHICH PARTICULARLY APPLY TO THIS MODEL......Page 295 Environmental Risks......Page 297 REFERENCES......Page 298 16. PSAMMOMYS OBESUS: PRIMARY INSULIN RESISTANCE LEADING TO NUTRITIONALLY INDUCED TYPE 2 DIABETES......Page 302 REFERENCES......Page 314 17. THE C57BL/6J MOUSE AS A MODEL OF DIET-INDUCED TYPE 2 DIABETES AND OBESITY......Page 317 SOURCES AND CARE OF RESEARCH SUBJECTS......Page 319 REFERENCES......Page 326 INDEX......Page 329 Autoimmune diabetes mellitus in the BB rat The NOD mouse and its related strains Obesity/diabetes in mice with mutations in the leptin or leptin receptor genes The Zucker Diabetic Fatty (ZDF) rat KK and KKAÞ mice The obese spontaneously hypertensive rat (SHROB, Koletsly rat): a model of metabolic syndrome X Characteristics of Wistar Fatty rat The New Zealand obese mouse: a polygenic model of type 2 diabetes The NSY mouse: an animal model of human type 2 diabetes mellitus with polygenic inheritance The Goto-Kakizaki rat The OLETF rat The JCR:LA-cp rat: an animal model of obesity and insulin resistance with spontaneous cardiovascular disease The neonatally streptozotocin-induced (n-STZ) diabetic rats, a family of NIDDM models Galactosemic animal models The rhesus monkey (Macac mulatta): a unique and valuable model for the study of spontaneous diabetes mellitus and associated conditions Psammomys obesus: primary insulin resistance leading to nutritionally induced type 2 diabetes The C57BL/6J mouse as a model of diet-induced type 2 diabetes and obesity.