Table Of ContentInsulin Resistance as a
Risk Factor in Visceral
and Neurological
Disorders
Insulin Resistance as a
Risk Factor in Visceral
and Neurological
Disorders
AKHLAQ A. FAROOQUI
Department of Molecular and CellularBiochemistry,
The Ohio State University, Columbus, OH, UnitedStates
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Dedication
This monograph is dedicated to my beloved father “late Sharafyab
Ahmed Sahab” whose guidance and influence continue to inspire and
support me.
Akhlaq A. Farooqui
Contents
Abouttheauthor xi
Preface xiii
Acknowledgments xvii
Listofabbreviations xix
1. Insulin resistance and obesity 1
Introduction 1
Insulinsignalinginthebrain 3
Insulinresistance 6
Insulinresistanceasaprotectivemechanism 21
Effectsofdietonmicrobiotapopulation 30
Microbiotaandshortchainfattyacids 34
Effectsofgutmicrobiotaandobesityonthebrain 38
Linkamonginsulinsignaling,obesity,andinsulinresistance 42
Contributionofleptininthedevelopmentofobesity 43
Contributionofadiponectininobesity 45
Insulinsignalingobesityandneurologicaldisorders 47
Conclusion 49
References 50
Furtherreading 69
2. Insulin resistance, diabetes, andmetabolic syndrome 71
Introduction 71
Biomarkersfortype2diabetes 77
miRNAs,diabetes,andvascularcomplications 78
Comlicationscausedbytype2diabetes 79
Molecularmechanismscontributingtotype2diabetescomplications 83
Riskfactorscontributingtometabolicsyndrome 88
Pathogenesisofmetabolicsyndrome 89
Linkbetweentype2diabetesandmetabolicsyndrome 92
Type2diabetesandmetabolicsyndromeasriskfactorsforAlzheimer’s
disease 94
Conclusion 100
References 101
Furtherreading 111
vii
viii Contents
3. Insulin resistance and heart disease 113
Introduction 113
Insulinsignalinginvasculature 121
Molecularmechanismofatherosclerosis 133
Carbohydratemetabolism,insulinresistance,andheartdisease 136
Biochemicallinksbetweeninsulinresistanceandheartdisease 140
Contributionoflipidmediatorsinheartdisease 140
Conclusion 143
References 144
Furtherreading 155
4. Insulin resistance and sleep apnea 157
Introduction 157
Obstructivesleepapnea 160
Biochemicalchangesinobstructivesleepapnea 162
Oxidativestress,insulinresistance,andobstructivesleepapnea 162
Obstructivesleepapnea(cid:1)mediatedchangesinlipidmetabolism 167
Inflammation,insulinresistance,andobstructivesleepapnea 168
Biomarkersforobstructivesleepapnea 170
Obstructivesleepapneaandheartdisease 172
Obstructivesleepapneaandhypertension 175
Obstructivesleepapneaandmetabolicsyndrome 176
Obstructivesleepapneaandstroke 179
Obstructivesleepapneaanditsrelationshipwithvariousdiseases 182
ObstructivesleepapneaandAlzheimer’sdisease 184
Obstructivesleepapneaanddepression 189
Conclusion 191
References 191
Furtherreading 205
5. Insulin resistance and stroke 207
Introduction 207
Hypertensionandpathogenesisofstroke 212
Contributionofdiet,microbiota,andinsulinresistanceinthepathogenesis
ofstroke 215
Stroke-mediatedchangesinthebrain 218
Molecularlinkamongadvancedglycatedendproducts,insulinresistance,
andstroke 230
Adipokines,insulinresistance,andstroke 233
Contents ix
Molecularlinkbetweenhypertensionandbraindamage 234
Effectofmicrobiotacompositiononstrokeoutcome 236
Conclusion 238
References 239
Furtherreading 248
6. Insulin resistance and Alzheimer’sdisease 249
Introduction 249
Insulinsignalinginthebrain 250
PathogenesisofAlzheimer’sdisease 255
Insulinreceptor,insulinsignaling,andinsulinresistanceinthebrain 264
Neurochemicallinksamonginsulinresistance,type2diabetes,and
Alzheimer’sdisease 265
Cerebralbloodflowintype2diabetesandAlzheimer’sdisease 271
Ceramode-mediatedinsulinresistanceintype2diabetesandAlzheimer’s
disease 273
Conclusion 277
References 278
Furtherreading 291
7. Insulin resistance and Parkinson’sdisease 293
Introduction 293
FamilialParkinson’sdisease 298
SporadicParkinson’sdisease 299
Gutmicrobiota,insulinresistance,andParkinson’sdisease 303
Insulinresistance,type2diabetes,andParkinson’sdisease 308
OverlapbetweenParkinson’sdiseaseandKrabbe’sdisease 316
OverlapbetweenParkinson’sdiseaseandGaucher’sdisease 318
BiomarkersforParkinson’sdisease 319
OxidativestressinParkinson’sdisease 320
NeuroinflammationinParkinson’sdisease 322
DepressionandParkinson’sdisease 324
Conclusion 326
References 327
Furtherreading 342
8. Insulin resistance, dementia, and depression 349
Introduction 349
Normalagingandcognitivefunction 352
x Contents
Neurochemicalaspectsofdementia 354
Classificationofdementias 355
Alzheimer’stypeofdementia 356
Neurochemicalaspectsofvasculardementia 359
NeurochemicalaspectsofLewybodydementia 361
Neurochemicalaspectsoffrontotemporaldementia 365
Insulinresistance,stress,anddepression 366
Effectsofdietandexerciseondementiaanddepression 373
Conclusion 374
References 374
Furtherreading 384
9. Use ofphytochemicals for the treatment of insulin
resistance(cid:1)linked visceral and neurologicaldisorders 385
Introduction 385
Effectsofvarioustypesofdietsoninsulinresistance 389
Effectsofcurcuminoninsulinresistanceandinsulinresistance(cid:1)linkeddiseases 400
Effectofgreenteaoninsulinresistance(cid:1)linkeddiseases 404
Effectofresveratroloninsulinresistanceandinsulinresistance(cid:1)linkeddiseases 407
Effectofn-3fattyacidsininsulinresistanceandinsulinresistance(cid:1)linked
diseases 413
Effectsofcinnamononinsulinresistanceandinsulinresistance(cid:1)linked
diseases 415
Effectsofgarliconinsulinresistanceandinsulinresistance(cid:1)linkeddiseases 419
Conclusion 424
References 425
Furtherreading 437
10. Summery and perspective for future research on insulin
resistance and insulin resistance(cid:1)linked visceral and
neurological disorders 439
Introduction 439
Chronicinsulinresistance:acommonlinkbetweenvisceralandneurological
disorders 443
Directionforfutureresearch 453
Conclusion 455
References 456
Index 463
About the author
Dr. Akhlaq A. Farooqui is a leader in the field of signal transduction,
brain phospholipases A , bioactive ether lipid metabolism, polyunsaturated
2
fatty acid metabolism, glycerophospholipid-, sphingolipid-, and
cholesterol-derived lipid mediators, glutamate-induced neurotoxicity, and
modulation of signal transduction by phytochemicals. He has discovered
the stimulation of plasmalogen-selective phospholipase A (PlsEtn-PLA )
2 2
and diacyl- and monoacylglycerol lipases in brains from patients with
Alzheimer’s disease. Stimulation of PlsEtn-PLA produces plasmalogen
2
deficiency and increases levels of eicosanoids that may be related to the
loss of synapses in brains of patients with Alzheimer’s disease. He has pub-
lished cutting edge research on the generation and identification of glycer-
ophospholipid-, sphingolipid-, and cholesterol-derived lipid mediators in
kainic acid(cid:1)mediated neurotoxicity by lipidomics. He has authored 12
monographs: Glycerophospholipids in Brain: Phospholipase A in Neurological
2
Disorders (2007); Neurochemical Aspects of Excitotoxicity (2008); Metabolism
and Functions of Bioactive Ether Lipids in Brain (2008); Hot Topics in Neural
Membrane Lipidology (2009); Beneficial Effects of Fish Oil in Human Brain
(2009); Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases
(2010); Lipid Mediators and their Metabolism in the Brain (2011);
Phytochemicals, Signal Transduction, and Neurological Disorders (2012);
Metabolic Syndrome: An Important Risk Factor for Stroke, Alzheimer’s Disease,
and Depression (2013); Inflammation and Oxidative Stress in Neurological
Disorders (2014); High Calorie Diet and the Human Brain (2015); and
Therapeutic Potentials of Curcumin For Alzheimer’s Disease (2016). All above
monographs have been published by Springer, New York and Springer
International Publishing Switzerland. Monographs on Neurochemical
Aspects of Alzheimer’s Disease (2017), Ischemic, Traumatic Brain, and Spinal
Cord Injuries: Mechanisms and Potential Therapies (2018), and Molecular
Mechanisms of Dementia: Biomarkers, Neurochemistry, and Therapy have been
published by Academic Press: An imprint of Elsevier, San Diego, CA.
In addition, he has edited 12 books: Biogenic Amines: Pharmacological,
Neurochemical and Molecular Aspects in the CNS (2010), Nova Science
Publisher, Hauppauge, New York; Molecular Aspects of Neurodegeneration
and Neuroprotection (2011), Bentham Science Publishers Ltd; Phytochemicals
and Human Health: Molecular and pharmacological Aspects (2011), Nova
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