Chapter Thirteen - Impaired Insulin Signaling and Mechanisms of Memory Loss.pdf.pdf

CHAPTER THIRTEEN
Impaired Insulin Signaling and
Mechanisms of Memory Loss
Jenna Bloemer1, Subhrajit Bhattacharya1, Rajesh Amin,
Vishnu Suppiramaniam
Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn,
Alabama, USA
1These authors contributed equally to this work.
Contents
1. Introduction 415
2. Diabetes and Cognitive Deficits 416
Type 1 diabetes mellitus 416
Type 2 diabetes mellitus 417
3. Central Insulin Regulation 417
The insulin signaling pathway 417
The source of insulin in the brain 419
Role of IRS-1 in central insulin resistance 419
4. Insulin Resistance and Hallmarks of Neurodegeneration 421
Tau pathology 421
Amyloid-b pathology 422
5. Common Mediators of Insulin Resistance and Cognitive Dysfunction 424
Advanced glycation end products 424
Mitochondrial dysfunction 424
Damage to the BBB 425
Formation of toxic lipids 425
Neuronal apoptosis 426
6. Insulin Resistance and Hippocampal Dysfunction 427
Regulation of cholinergic neurons 427
Synaptic plasticity 428
7. Role of IGF in Cognitive Function 429
IGF-1, insulin, and cognitive impairment 429
Neuroprotective effects of IGF-1 429
Therapeutic implications of IGF-1 430
8. Animal Models of Insulin Signaling Deficits 430
NIRKO model 430
db/db model 431
STZ-diabetic model 431
Intracerebral STZ model 432
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Progress in Molecular Biology and Translational Science, Volume 121 2014 Elsevier Inc. 413
ISSN 1877-1173 All rights reserved.
http://dx./-0-12-800101--2
414 Jenna Bloemer et al.
9. Role of Antidiabetes Drugs in the Treatment of Cognitive Dysfunction 432
Insulin 432
PPAR agonists 434
GLP-1R agonists 435
10. Summary 435
Acknowledgments 436
References 436
Abstract
Insulin is secreted from the b-cells of the pancreas and helps maintain glucose homeo-
stasis. Although secreted peripher