Chronic Complications in Diabetes: Animal Models and Chronic Complications (Frontiers in Animal Diabetes Research,)

Individual volumes in the series Frontiers in Animal Diabetes Research provide basic researchers as well as clinical investigators with in-depth coverage of basic experimental diabetes research. Each volume will be topic oriented with timely and liberally referenced reviews. The series will provide a valuable reference source for basic researchers as well as clinical investigators, graduate students and research fellows in the areas of diabetology, endocrinology, physiology, and pharmacology. Major advances have been made in diabetes research, partly as a result of experimentation in animal models. Experimental animal research has contributed significantly to the understanding of the aetiology of this disease and its dreaded complications. In particular the areas of immunology, insulin signal transduction, and the pathogenetic mechanisms involved in the chronic complications have become clearer. Various animal models used in diabetes research are reviewed, together with the diverse but often interrelated mechanism in the complication of diabetes. The functional and structural consequences in the various target organs are also discussed. Students, trainees, fellows, as well as clinicians and investigators interested in diabetes and its complications will find this new book series a valuable reference source. BOOK COVER......Page 1 HALF-TITLE......Page 2 SERIES-TITLE......Page 3 TITLE......Page 4 COPYRIGHT......Page 5 CONTENTS......Page 6 PREFACE TO THE SERIES......Page 8 PREFACE......Page 9 CONTRIBUTORS......Page 10 NEPHROPATHY......Page 12 Comparison of Human and Animal Morphological Kidney Changes in Diabetes......Page 14 Models of type 1 diabetes......Page 16 Hyperinsulinemic and insulin resistant animal species......Page 17 Cataract Lesions......Page 21 Retinopathy......Page 23 NCV Slowing and the Polyol Pathway; Role of Aldose Reductase and its Inhibitors......Page 26 Nerve Hypoxia-Ischemia, Oxidative Stress and Prostacyclin Effects in Diabetic Animals......Page 28 Glycation of Nerve Components and its Prevention......Page 29 Neuropathy in Other Animal Models......Page 30 REFERENCES......Page 32 INTRODUCTION......Page 56 PRODUCTS AND PATHWAYS OF THE MAILLARD REACTION......Page 57 THE STREPTOZOTOCIN-INDUCED DIABETIC RAT AND MOUSE MODELS......Page 60 EVALUATION OF THE AGE HYPOTHESIS IN THE STZ-RAT MODEL......Page 61 CHEMICAL AND IMMUNOLOGICAL ASSAYS FOR AGEs......Page 63 INHIBITION OF AGE FORMATION......Page 65 CYTOTOXICITY OF AGE-PROTEINS IN NON-DIABETIC RATS......Page 66 RECEPTORS FOR AGE-PROTEINS......Page 68 AGES AND OXIDATIVE STRESS......Page 70 SUMMARY AND CONCLUSIONS......Page 71 REFERENCES......Page 72 INTRODUCTION......Page 84 Viral Antigens......Page 85 Cytokine Expression in β-cells of Transgenic Mice......Page 87 NOD Transgenic Mice......Page 88 NON-INSULIN DEPENDENT DIABETES MELLITUS (NIDDM) MODEL......Page 89 Glucokinase (GK) Gene......Page 90 Glucose Transporter Gene......Page 92 Genes of Calmodulin, Insulin Receptor Substrate-1 and Insulin Receptor......Page 93 Growth Factors like Growth Hormone (GH) and Insulin-like Growth Factor (IGF)......Page 94 Mutant GH Gene......Page 96 Aldose Reductase (AR) Gene......Page 98 ACKNOWLEDGMENT......Page 101 REFERENCES......Page 102 Reactive Oxygen Species and Cell Damage......Page 110 Free Radical Defense Mechanisms......Page 111 Vascular Actions of Reactive Oxygen Species in Diabetes and Effects of Antioxidant Treatment......Page 112 Roles of Advanced Glycation and the Polyol Pathway in Oxidative Stress......Page 119 Essential Fatty Acids and Neurovascular Dysfunction......Page 122 Non-vascular Effects of Essential Fatty Acids......Page 125 Carnitine Metabolism, Vascular Function and Diabetic Complications......Page 126 INTERACTIONS BETWEEN OXIDATIVE STRESS AND FATTY ACID MECHANISMS......Page 127 SUMMARY AND CONCLUSIONS......Page 130 REFERENCES......Page 131 Alloxan and Streptozotocin......Page 144 Histopathology......Page 145 Dosages......Page 146 Large Animal Models......Page 147 CHANGES IN NERVE CONDUCTION......Page 148 The Role of Myoinositol......Page 149 THE EFFECTS OF ALDOSE REDUCTASE INHIBITION......Page 150 EFFECTS OF ISCHAEMIA......Page 151 Anterior Horn and Dorsal Root Ganglion Cells......Page 152 Nerve Trunks......Page 153 Conventional Insulin Treatment (CIT)......Page 154 Aldose Reductase Inhibition......Page 156 Pancreatic Islet Transplantation......Page 158 The db/db Mouse......Page 159 The Spontaneously Diabetic BB Wistar Rat......Page 160 Other Spontaneously Diabetic Animal Models......Page 162 REFERENCES......Page 163 BACKGROUND......Page 180 PRODUCTION AND ACTION OF NEUROTROPHINS IN DIABETES......Page 182 OTHER NEUROTROPHINS......Page 189 CONCLUSIONS......Page 191 REFERENCES......Page 192 BACKGROUND......Page 196 EVIDENCE THAT DIABETES-ASSOCIATED MYOPATHY INVOLVES ALTERED REGULATION OF BASAL CYTOSOLIC CALCIUM LEVELS......Page 197 Gastrointestinal Smooth Muscle......Page 198 Cardiovascular Muscle......Page 199 DIABETIC NEUROPATHY......Page 200 Diabetic Neuropathy is Associated with Altered Calcium Signaling in Primary Sensory Neurons......Page 201 Diabetic Neuropathy: Role of Vasoactive Agents......Page 202 Diabetic Neuropathy: Role of Neurotrophic Growth Factors......Page 203 Potential Sites of Defective Calcium Regulation in Diabetes......Page 205 SUMMARY AND CONCLUSIONS......Page 206 REFERENCES......Page 208 MODELS OF EXPERIMENTAL DIABETES......Page 214 GLYCEMIC CONTROL AND DIABETIC NEPHROPATHY......Page 216 RENAL FUNCTIONAL ABNORMALITIES IN EXPERIMENTAL DIABETES......Page 217 MOLECULAR BIOLOGICAL STUDIES OF THE DIABETIC KIDNEY......Page 219 TREATMENT OF EXPERIMENTAL DIABETIC NEPHROPATHY......Page 221 REFERENCES......Page 227 HUMAN DIABETIC RETINOPATHY......Page 240 Pathologic Features of Human Diabetic Retinopathy......Page 241 Pathogenesis of Human Diabetic Retinopathy......Page 242 Diabetic dogs......Page 243 Diabetic rats......Page 244 Other diabetic animal models......Page 245 Polyol pathway......Page 247 Redox imbalance......Page 248 Non-enzymatic glycation......Page 249 Retinal Functional Alteration in Animal Models......Page 250 What Have We Learned So Far from Animal Experiments?......Page 251 Where We Go from Here?......Page 252 REFERENCES......Page 253 10. FETAL MALFORMATIONS IN DIABETES......Page 262 Hyperglycemia......Page 263 Increased Flux in the Polyol Pathway......Page 265 Hyperketonemia......Page 266 Excess Radical Oxygen Species (ROS)......Page 267 Altered Metabolism of Arachidonic Acid and Prostaglandins......Page 268 Production of Reactive Oxo-Aldehydes......Page 269 Alterations in Gene Expression......Page 270 In vitro Treatment......Page 271 In vivo Treatment......Page 272 REFERENCES......Page 273 INDEX......Page 282 Machine generated contents note: 1 Diabetic Animals for Research into the Complications: A General Overview 1 Eleazar Shafrir and Anders A.F Sima 2 Studies in Animal Models on the Role of Glycation and Advanced Glycation End-Products (AGEs) in the Pathogenesis of Diabetic Complications: Pitfalls and Limitations 43 Jesds R. Requena and John W Baynes 3 Utility of the Transgenic Mouse in Diabetes Research 71 Soroku Yagihashi, Shin-lchiro Yamagishi and Chihiro Nishimura 4 Oxidative Stress and Abnormal Lipid Metabolism in Diabetic Complications 97 Norman E. Cameron and Mary A. Cotter 5 Diabetic Neuropathy in Various Animal Models 131 Ashutosh K. Sharma and Penelope A. Richards 6 Neurotrophism in Diabetic Neuropathy 167 David R. Tomlinson and Paul Fernyhough 7 Diabetes Mellitus: Evidence for Altered Calcium Signaling in Excitable Tissues 183 Karen E. Hall andJohn W Wiley 8 Experimental Diabetic Nephropathy 203 Mark E. Cooper, Richard E. Gilbert, Darren J. Kelly and Terri J. Allen 9 Diabetic Retinopathy in Experimental Animal Models and their Feasibility for Understanding the Human Disease 229 Subrata Chakrabarti 10 Fetal Malformations in Diabetes 251 UlfJ. Eriksson. Individual volumes in the series Frontiers in Animal Diabetes Research provide basic researchers as well as clinical investigators with in-depth coverage of basic experimental diabetes research. Each volume will be topic oriented with timely and liberally referenced reviews. The book provides a valuable reference source for basic researchers as well as clinical investigators, graduate students and research fellows in the areas of diabetology, endocrinology, physiology, and pharmacology.