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

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