The Metabolic Syndrome: Epidemiology, Clinical Treatment, and Underlying Mechanisms (Contemporary Endocrinology)

The Metabolic Syndrome: Epidemiology, Clinical Treatment, and Underlying Mechanisms (Contemporary Endocrinology)......Page 1
Front-matter......Page 2
Title Page
......Page 4
Copyright Page
......Page 5
PREFACE......Page 6
REFERENCES......Page 7
Table of Contents (with page links in titles & page numbers)......Page 8
CONTRIBUTORS......Page 10
COLOR PLATES......Page 12
BACKGROUND......Page 14
NATURAL HISTORY......Page 15
CHAPTER SUMMARIES......Page 16
REFERENCES......Page 18
I.
Epidemilogy And Clinical Treatment: Issues In Defining And Treating The Metabolic Syndrome......Page 21
INTRODUCTION......Page 22
IT'S A BIRD! IT'S A PlANE! IT'S THE METABOLIC SYNDROME!......Page 23
WHAT IS THE RELATIONSHIP AMONG THE METABOLIC SYNDROME DIAGNOSTIC CRITERIA: CASUAL OR CAUSAL?
......Page 26
Dyslipidemia......Page 27
POSTPRANDIAL LIPEMIA......Page 28
ATHEROGENIC LIPOPROTEINS AND INSULIN RESISTANCE......Page 29
Blood Pressure......Page 30
Insulin Resistance and Procoagulant and Proinflammatory Factors......Page 31
Obesity and Insulin-Mediated Glucose Uptake (IMGU)......Page 32
WC versus BMI as Predictors of IMGU
......Page 33
Relationship Among Adiposity, Insulin Resistance, and CVD Risk......Page 34
INTERACTION AMONG BMI, INSULIN ACTION, AND CVD RISK FACTORS......Page 35
OBESITY DOES NOT NECESSARILY TRANSLATE INTO INCREASED CVD RISK......Page 36
Visceral Obesity and Insulin Resistance......Page 37
Visceral Fat and Adverse Clinical Outcomes......Page 39
IS THERE CLINICAL UTILITY IN DIAGNOSING THE METS?......Page 40
REFERENCES......Page 42
OVERVIEW......Page 48
METABOLIC SYNDROME AND OBESITY......Page 49
THE ROLE OF OBESITY IN RISK FACTOR CLUSTERING AND METABOLIC SYNDROME
......Page 50
MECHANISMS FOR RISK FACTOR CLUSTERING ASSOCIATED WITH OBESITY
......Page 51
TREATMENT OPTIONS TO REDUCE RISK FACTOR CLUSTERING ASSOCIATED WITH OBESITY
......Page 55
REFERENCES......Page 57
INTRODUCTION......Page 67
Effects of Weight Loss on Central Adiposity......Page 68
Exercise and Loss of Body Weight and Visceral Fat......Page 69
RIMONABANT......Page 71
ORLISTAT......Page 73
SIBUTRAMINE......Page 74
LAPAROSCOPIC PLACEMENT OF A GASTRIC BAND......Page 76
LIPOSUCTION AND OMENTECTOMY......Page 77
Testosterone and Anabolic Steroids......Page 78
CONCLUSION......Page 79
REFERENCES......Page 80
INSULIN RESISTANCE AND SURROGATE MEASURES FOR INSULIN RESISTANCE
......Page 84
THE METABOLIC SYNDROME AND CARDIOVASCULAR DISEASE......Page 87
MECHANISMS......Page 88
REFERENCES......Page 89
6 The Sympatho-Adrenal System in the Metabolic Syndrome
......Page 94
SYMPATHETIC NERVOUS SYSTEM (SNS) ACTIVITY IS INCREASED IN THE METABOLIC SYNDROME
......Page 95
Insulin Stimulates the SNS......Page 96
LEPTIN STIMULATES SNS ACTIVITY......Page 97
Insulin Mediates Dietary Changes in SNS Activity......Page 98
THE ADAPTIVE SIGNIFICANCE OF INSULIN RESISTANCE......Page 99
Insulin Resistance as a Compensatory Mechanism......Page 100
INCREASED SYMPATHETIC ACTIVITY IN OBESITY DEPENDS ON INSULIN AND IS LINKED TO BLOOD PRESSURE
......Page 101
CAN INCREASED SNS ACTIVITY BE THE PRIMARY ABNORMALITY IN THE METABOLIC SYNDROME?
......Page 102
Evidence Against a Primary Role for the SNS......Page 103
Low Levels of Epinephrine Are Related to High Triglyceride and Low HDL-Cholesterol Levels
......Page 104
SLEEP DEBT Is ASSOCIATED WITH INCREASED CORTISOL LEVELS AND INSULIN RESISTANCE
......Page 106
DIETARY RECOMMENDATIONS......Page 107
CONCLUSIONS: FEAST OR FAMINE-THE LEGACY OF THRIFTY METABOLIC TRAITS IN THE FACE OF AN ABUNDANT FOOD SUPPLY
......Page 108
REFERENCES......Page 109
II.
Endothelial Function, Inflammation, and Dyslipidemia......Page 114
INTRODUCTION......Page 115
INSULIN RECEPTOR TYROSINE KINASE......Page 116
PHOSPHATIDYLINOSITOL 3-KINASE......Page 117
CHARACTERISTIC FEATURES OF ENOS ACTIVATION IN RESPONSE TO INSULIN......Page 118
Insulin-Stimulated Secretion of ET-1
......Page 119
Insulin and Nitric Oxide-Dependent Vasodilation......Page 120
PARALLEL INSULIN SIGNALING PATHWAYS IN METABOLIC AND VASCULAR TISSUES
......Page 123
Integrated Actions of Insulin in Skeletal Muscle Beds......Page 124
Insulin Resistance Couples Vascular and Metabolic Pathophysiology......Page 125
GENERALIZED VASCULAR DYSFUNCTION IN INSULIN RESISTANCE
......Page 126
Insulin and Endothelin Action in the Vasculature......Page 129
Pharmacological Therapies Targeting Insulin Resistance......Page 132
Pharmacological Therapies Targeting Endothelial Dysfunction......Page 133
REFERENCES......Page 135
INTRODUCTION......Page 144
The cp (Corpulent) Gene......Page 145
The fa (Fatty) Gene......Page 146
MACROVASCULAR DISEASE......Page 147
Thrombosis......Page 148
Vasculopathy......Page 149
Vascular Smooth Muscle Cells......Page 152
Insulin Resistance......Page 154
Hyperlipdemia......Page 156
Cytokines and Vascular Disease Risk......Page 157
HORMONAL STATUS AND POLYCYSTIC OVARY DISEASE......Page 158
INTERVENTIONS......Page 160
α-Glucosidase Inhibitors
......Page 161
Dietary Components and Supplements......Page 162
Anorectic/Insulin-Sensitizing Pharmaceutical Agents......Page 164
Nitric Oxide Metabolism......Page 165
Calcium Channel Antagonists......Page 166
Environmental Stress and Toxic Agents......Page 167
REFERENCES......Page 168
ABSTRACT......Page 174
C-REACTIVE PROTEIN (CRP): BIOLOGICAL PROPERTIES AND CLINICAL USE
......Page 175
CRP and Obesity......Page 176
CRP and Glucose Homeostasis......Page 179
CRP and Hypertension......Page 180
CRP and Lipid Metabolism......Page 181
CRP AND THE PREVALENCE AND INCIDENCE OF METABOLIC SYNDROME: EPIDEMIOLOGICAL EVIDENCE
......Page 182
COMPARISON OF THE PREDICTIVE VALUES OF CRP AND THE METABOLIC SYNDROME ON CARDIOVASCULAR AND DIABETES RISK
......Page 186
IMPLICATIONS AND FUTURE RESEARCH......Page 187
REFERENCES......Page 189
FIRST-DEGREE RELATIVES OF TYPE 2 DIABETIC PATIENTS AND RISK OF DIABETES
......Page 196
Evidence of Dysregulated Adipose Tissue in First-Degree Relatives and Insulin Resistance
......Page 197
Insulin Signaling Leading to Glucose Uptake and Other Effects in Adipose Cells
......Page 198
Adipose Tissue Is Dysregulated in Insulin Resistance and Type 2 Diabetes Effectson Insulin Signaling and Adipocyte Function
......Page 200
ADIPOSE TISSUE AND INFLAMMATION......Page 201
Inflammatory Markers CRP and SAA
......Page 203
THIAZOLIDINEDIONES......Page 204
REFERENCES......Page 205
EPIDEMIOLOGY OF DYSLIPIDEMIA AND INSULIN RESISTANCE......Page 212
NORMAL LIPID AND LIPOPROTEIN PHYSIOLOGY......Page 213
Overproduction of VLDL......Page 217
Defective VWL, Remnant, and LDL Catabolism......Page 218
Generation of Small, DenseWL......Page 219
Increased Catabolism of HDL
......Page 220
Postprandial Hyperlipidemia......Page 221
SUMMARY......Page 222
REFERENCES......Page 223
III.
Insulin—Secretion and Action: Underlying Mechanisms of the Metabolic Syndrome......Page 226
OBESITY AND PANCREATIC FAT......Page 227
OBESITY AND PANCREATIC ISLET FUNCTION......Page 229
Effects of Sustained Hyperlipidemia on Insulin Secretion......Page 230
Beta Cell Lipoapoptosis and the Role of Saturated NEFAs......Page 231
LIPIDS, INSULIN RESISTANCE, AND ISLET AMYLOID FORMATION......Page 232
REFERENCES......Page 234
ABSTRACT......Page 239
GLUCAGON-LIKE PEPTIDES......Page 240
EXPRESSION OF THE GLUCAGON GENE......Page 241
EXPRESSION OF THE RECEPTORS FOR THE GLUCAGON-LIKE PEPTIDES
......Page 243
Effects on the Islets......Page 244
Effects on the Gastrointestinal Tract......Page 245
Other Actions......Page 246
ACTIONS OF GLP-2......Page 247
EFFECTS OF GLP-I ON INSULIN ACTION......Page 248
Therapeutic Application of Proglucagon-Derived Peptides
......Page 251
REFERENCES......Page 252
INTRODUCTION......Page 261
THE MAMMALIAN INSULIN/IGF1 RECEPTOR TYROSINE KINASES
......Page 262
INSULIN/IGF SIGNALING: THE BASICS......Page 263
IRS2 SIGNALING REVEALS THE LINK BETWEEN PERIPHERAL INSULIN ACTION AND PANCREATIC ß-CELL FUNCTION
......Page 265
INSULIN SIGNALING IN HEPATIC METABOLISM......Page 269
Introduction......Page 271
Multisite SIT-Phosphorylation of IRS-Proteins......Page 272
IRS-PROTEIN DEGRADATION......Page 273
THE RELATION BETWEEN GLP1 AND IRS2 SIGNALING
......Page 274
SUMMARY AND PERSPECTIVE......Page 275
REFERENCES......Page 276
INSULIN RESISTANCE......Page 284
INSULIN SIGNALING PATHWAY......Page 285
THE INSULIN RECEPTOR......Page 287
Functional Aspects of IR Structure......Page 288
STRUCTURAL ASPECTS OF IR AUTOPHOSPHORYLATION......Page 289
FUNCTIONAL ASPECTS OF IR TYROSINE KINASE ACTIVITY......Page 290
INSULIN RECEPTOR FUNCTION IN INSULIN RESISTANCE......Page 292
Diet......Page 293
Inherited Insulin Resistance......Page 294
Pregnancy......Page 295
TYROSINE PHOSPHATASES......Page 296
PC-1
......Page 297
PROTEIN KINASE C-MEDIATED SERINE PHOSPHORYLATION......Page 299
CYTOKINE ACTIVATED SERINE KINASES......Page 301
REFERENCES......Page 302
INTRODUCTION......Page 311
OVERVIEW OF LIPID METABOLISM AND INSULIN RESISTANCE......Page 312
ACUTE FATTY ACID ELEVATION CAN CAUSE MUSCLE INSULIN RESISTANCE
......Page 313
Animal Studies......Page 314
Human Studies......Page 315
Long-Chain Acyl CoAs......Page 316
DAGs and Ceramides......Page 317
Muscle Membrane Composition......Page 318
ADIPOSE BODY DEPOTS AND FFA FLUXES TO MUSCLE......Page 319
CYfOKINES AND INFLAMMATORY PATHWAYS: AN ADDITIONAL COMPONENT OF MUSCLE INSULIN RESISTANCE IN OBESITY AND TYPE 2 DIABETES
......Page 320
PHARMACOLOGICAL MANIPULATION OF MUSCLE LIPID ACCUMULATION
......Page 321
PPARγ Agonists
......Page 322
PPARα Agonists
......Page 323
REFERENCES......Page 324
INTRODUCTORY OVERVIEW......Page 333
GENERAL ASPECTS OF INSULIN SIGNALING......Page 334
TISSUE-SPECIFIC DIFFERENCES IN UPSTREAM ACTIVATORS OF aPKC AND PKB......Page 336
INSULIN SIGNALING DEFECTS IN MUSCLE AND ADIPOSE TISSUE IN TYPE 2 DIABETES
......Page 337
INSULIN SIGNALING DEFECTS IN MUSCLE IN OBESITY......Page 338
INSULIN SIGNALING IN LIVERS OF DIABETIC RODENTS......Page 339
METABOLIC CONSEQUENCES OF DIVERGENT ALTERATIONS OF INSULIN SIGNALING IN MUSCLE AND LIVER IN OBESITY AND DIABETES
......Page 340
Exercise......Page 341
Thiazolidinediones......Page 342
REFERENCES......Page 343
INTRODUCTION......Page 347
THE BIOLOGY OF DIABETES: FOCUS ON HYPERGLYCEMIA......Page 348
Pathophysiology......Page 349
Glucose Levels and Fluxes......Page 350
Free Fatty Acids and Hormones......Page 352
Postprandial Suppression of Endogenous Glucose Production in Normal Controls and Type 2 Diabetic Subjects
......Page 353
HEPATIC INSULIN ACTION AND THE METABOLIC MACHINERY UNDERLYING GLUCOSE METABOLISM IN THE LIVER
......Page 356
Glucogenic Metabolite Fluxes: Glycogenic Substrates and Signals......Page 357
Links Between Gluconeogenesis and Hepatic Glycogen in Type 2 Diabetes......Page 358
GLUCOSE PRODUCTION......Page 359
GLUCOSE UPTAKE......Page 360
GLUCOSE-LIPID INTERACTIONS, REGULATION BY INSULIN, AND TYPE 2 DIABETES
......Page 361
Metabolic Zonation: The Effects of O2 and Nonalcoholic Steatohepatitis
......Page 362
Theoretical Approaches......Page 363
REFERENCES......Page 365
A LONG LOOK BACK......Page 380
KEY FEATURES OF THE METABOLIC SYNDROME: A REDUCTIONIST APPROACH FOR THE EPIDEMIOLOGIST OR FOR THE CLINICAL PRACTITIONER
......Page 381
THE COMPLEXITY OF THE METABOLIC SYNDROME: PATTERN RECOGNITION
......Page 384
THE LONGITUDINAL DEVELOPMENT OF THE METABOLIC SYNDROME
......Page 386
REFERENCES......Page 390
INDEX......Page 394