Insulin resistance : insulin action and its disturbances in disease / editors, Sudhesh Kumar, Stephen O'Rahilly.

Format:

Book

Contributor:

Kumar, Sudhesh.

O'Rahilly, S. (Stephen)

Alumni and Friends Memorial Book Fund.

Language:

English

Subjects (All):

Insulin resistance.

Insulin Resistance.

Medical Subjects:

Insulin Resistance.

Physical Description:

xv, 599 pages : illustrations ; 24 cm

Place of Publication:

Chichester, West Sussex, England ; Hoboken, N.J. : J. Wiley, [2005]

Summary:

Insulin resistance is a key abnormality associated with a number of common metabolic and cardiovascular diseases, including Type 2 diabetes and obesity. This has therefore been an area of intense scrutiny for researchers worldwide. Over the last decade in particular, a plethora of defining studies have helped to cast light on both the clinical and the molecular aspects of insulin resistance. Firstly, study of rare syndromes of severe insulin resistance has led to better definition of these conditions and, in many cases, to a better understanding of the molecular basis of these diseases. Secondly, the importance of insulin resistance to the development and progression of common diseases such as Type 2 diabetes, polycystic ovarian syndrome, cardiovascular disease and obesity is better appreciated. Thirdly, we now have drugs that can reduce insulin resistance significantly and this has had an impact on both basic and clinical research in the field. Consequently, we are beginning to see a major paradigm shift in how Type 2 diabetes and the metabolic syndrome are being managed, with a greater emphasis on addressing insulin resistance than ever before.

In this book, several leading investigators who have made seminal contributions to the field have written chapters covering the normal biology of insulin action, the pathophysiology of insulin resistance, the myriad clinical consequences of insulin resistance, and finally, current and future prospects for its treatment. The book therefore not only provides an up-to-date perspective of the subject from several of the leading thinkers in the field, but should also serve as a useful source of reference for students, researchers and clinicians.

Contents:

1 The Insulin Receptor and Downstream Signalling / Ken Siddle 1

1.2 Insulin receptor structure and function 2

1.3 Insulin receptor substrates 15

1.4 Downstream signalling pathways 23

1.5 The basis of insulin's signalling specificity 37

2 Insulin-mediated Regulation of Glucose Metabolism / Daniel Konrad, Assaf Rudich, Amira Klip 63

2.2 Insulin as a master regulator of whole body glucose disposal 63

2.3 Insulin-mediated regulation of glucose metabolic pathways 67

2.4 Glucose uptake into skeletal muscle - the rate-limiting step in glucose metabolism 69

3 Insulin Action on Lipid Metabolism / Keith N. Frayn, Fredrik Karpe 87

3.1 Introduction: does insulin affect lipid metabolism? 87

3.2 Molecular mechanisms by which insulin regulates lipid metabolism 88

3.3 Insulin and lipolysis 89

3.4 Insulin, lipoprotein lipase and cellular fatty acid uptake 94

3.5 Co-ordinated regulation of fatty acid synthesis and ketogenesis 96

3.6 Insulin and cholesterol synthesis 97

3.7 Insulin effects on lipoprotein metabolism 98

4 The Effect of Insulin on Protein Metabolism / Laura J. S. Greenlund, K. Sreekumaran Nair 105

4.2 Molecular mechanisms of insulin's effect on protein turnover 107

4.3 Measurement of protein metabolism (synthesis and breakdown or turnover) in human subjects 111

4.4 Whole body and regional protein turnover 114

5 Genetically Modified Mouse Models of Insulin Resistance / Gema Medina-Gomez, Christopher Lelliott, Antonio J. Vidal-Puig 133

5.2 Genetic modification as a tool to dissect the mechanisms leading to insulin resistance 134

5.3 Candidate genes involved in the mechanisms of insulin resistance 134

5.4 Insulin signalling network 136

5.5 Factors leading to insulin resistance 137

5.6 Defining the function of the insulin cascade molecules through global knockouts 137

5.7 Double heterozygous mice as models of polygenic forms of diabetes 139

5.8 Defining tissue and/or organ relevance for the maintenance of insulin sensitivity 140

5.9 Genetically modified mice to study modulators of insulin sensitivity 142

5.10 Lipodystrophy versus obesity, the insulin resistance paradox 143

5.11 Excess of nutrients as a cause of insulin resistance 147

5.12 PPARs, key mediators of nutritional-regulated gene expression and insulin sensitivity 148

6 Insulin Resistance in Glucose Disposal and Production in Man with Specific Reference to Metabolic Syndrome and Type 2 Diabetes / Henning Beck-Nielsen, Frank Alford, Ole Hother-Nielsen 155

6.2 Measurement of insulin resistance 157

6.3 Insulin-resistant states 162

6.4 Conclusion and perspectives 171

7 Central Regulation of Peripheral Glucose Metabolism / Stanley M. Hileman, Christian Bjorbaek 179

7.2 Counter-regulation of hypoglycaemia - role of the CNS 180

7.3 Brain regions involved in counter-regulation 182

7.4 Glucosensing neurons 184

7.5 Central control of peripheral organs involved in glucoregulation 187

7.6 Additional afferent signals to the CNS regulating peripheral glucose metabolism 189

7.7 Conclusions and future perspectives 194

8 Relationship between Fat Distribution and Insulin Resistance / Philip G. McTernan, Aresh Anwar, Sudhesh Kumar 207

8.2 Fat and its distribution 207

8.3 Basis for variation in adipose tissue mass 209

8.4 Change in adipocyte phenotype with obesity 210

8.5 Obesity and its association with insulin resistance 210

8.6 Subcutaneous and visceral adipose tissue 211

8.7 The pathogenic significance of abdominal adipose tissue 211

8.8 Potential mechanisms linking central obesity to the metabolic syndrome 212

8.9 Randle hypothesis/glucose-fatty acid hypothesis 212

8.10 Alternatives to the Randle hypothesis 213

8.11 Ectopic fat storage: fat content in obesity 214

8.12 Adipose tissue as an endocrine organ 214

8.13 Plasminogen activator-inhibitor 1 215

8.14 Renin angiotensin system in adipose tissue 216

8.15 Visceral obesity and steroid hormone metabolism 217

8.16 Glucocorticoid metabolism and obesity 217

8.17 11[beta]-hydroxysteroid dehydrogenase (11[beta]-HSD) 218

8.18 Isoenzymes of 11[beta]-HSD 218

8.19 11[beta]-HSD and obesity 219

8.20 Sex steroid metabolism and obesity: oestrogen biosynthesis 220

8.21 Aromatase 220

8.22 Sex steroids and body fat 222

9 PPAR[gamma] and Glucose Homeostasis / Robert K. Semple, Stephen O'Rahilly 237

9.1 Evidence from cell and rodent models 238

9.2 Insights from human studies 251

10 Adipokines and Insulin Resistance / Daniel K. Clarke, Vidya Mohamed-Ali 269

10.1 Obesity and insulin resistance 270

10.2 Adipokines implicated in insulin resistance 272

11 Dietary Factors and Insulin Resistance / Jeremy Krebs, Susan Jebb 297

11.2 The importance of body fatness 298

11.3 Specific dietary factors 302

12 Physical Activity and Insulin Resistance / Nicholas J. Wareham, Soren Brage, Paul W. Franks, Rebecca A. Abbott 317

12.2 Evidence from observational studies of the association between physical activity and insulin resistance 318

12.3 Summary of findings from observational studies in adults 318

12.4 Summary of findings from observational studies in children and adolescents 340

12.5 Mechanisms underlying the association between physical activity and insulin resistance 351

12.6 Trials of the effect of physical activity on insulin sensitivity in adults 353

12.7 Trials of the effect of physical activity on insulin sensitivity in children and adolescents 374

12.8 Evidence of heterogeneity of the effect of physical inactivity on insulin resistance in sub-groups of the population 375

13 Genetics of the Metabolic Syndrome / George Argyropoulos, Steven Smith, Claude Bouchard 401

13.1 Historical perspective 401

13.2 Pathophysiology 404

13.3 Genetic epidemiology 407

13.4 Monogenic disorders 411

13.5 Candidate genes 414

13.6 Genomic scans 426

14 Insulin Resistance and Dyslipidaemia / Benoit Lamarche, Jean-Francois Mauger 451

14.2 Historical notes 451

14.3 Obesity versus the insulin resistance syndrome 453

14.4 Hypertriglyceridaemia 453

14.5 Reduced HDL cholesterol concentrations 455

14.6 Small, dense LDL particles 457

14.7 LDL cholesterol levels versus LDL particle number 459

14.8 Insulin resistance, dyslipidaemia and the risk of cardiovascular disease 460

15 Insulin Resistance, Hypertension and Endothelial Dysfunction / Stephen J. Cleland, John M. C.

Connell 467

15.2 Hyperinsulinaemia, insulin resistance and hypertension 467

15.3 Possible mechanisms linking insulin with blood pressure 468

15.4 Atherosclerosis and insulin resistance 469

15.5 Vascular endothelial dysfunction and mechanisms of atherothrombotic disease 469

15.6 Direct vascular action of insulin 471

15.7 What causes abnormal insulin signalling in metabolic and vascular tissues? 474

15.8 Summary and conclusions (Figure 15.8) 477

16 Insulin Resistance and Polycystic Ovary Syndrome / Neus Potau 485

16.2 Definition of polycystic ovary syndrome (PCOS) and diagnostic criteria 486

16.3 Hyperandrogenism and hyperinsulinism 489

16.4 Assessment of insulin resistance in PCOS 491

16.5 Gene studies on PCOS 492

16.6 Premature pubarche, hyperinsulinism and PCOS 495

16.7 Treatment approach with antiandrogens 497

16.8 Treatment approach with insulin sensitizers (metformin) 498

16.9 Treatment approach with insulin sensitizers (thiazolidinediones) 501

17 Syndromes of Severe Insulin Resistance (SSIRs) / David Savage, Stephen O'Rahilly 511

17.2 General biochemical and clinical features of severe insulin resistance 512

17.3 Classification of specific syndromes of insulin resistance 514

17.4 Primary disorders of insulin action 515

17.5 Lipodystrophic syndromes and a lipocentric approach to diabetes 518

17.6 Complex genetic syndromes associated with severe insulin resistance 525

17.7 Therapeutic options in the syndromes of severe insulin resistance 526

18 Therapeutic Strategies for Insulin Resistance / Harpal S. Randeva, Margaret Clarke, Sudhesh Kumar 535

18.2 Obesity and insulin resistance 535

18.3 Management of obesity 537

18.4 Dietary management of obesity 539

18.5 Exercise and physical activity 540

18.6 Anti-obesity drugs 540

18.7 Surgical management of obesity 543

18.8 Pharmacological treatment of insulin resistance 544

18.9 Insulin sensitizers and cardiovascular risk factors 551

19 Drug Therapy for Insulin Resistance - a Look at the Future / Bei B. Zhang, David E. Moller 561

19.2 Targeting molecules within the insulin signal transduction pathway 563

19.3 Targeting negative modulators of insulin signalling 567

19.4 Targeting obesity and insulin resistance 569.

Notes:

Includes bibliographical references and index.

Local Notes:

Acquired for the Penn Libraries with assistance from the Alumni and Friends Memorial Book Fund.

ISBN:

0470850086

9780470850084

OCLC:

56012344

Online:

Publisher description

Book review (E-STREAMS)