Physiological Consequences of Brain Insulin Action

Cover
Half Title
Series Page
Title Page
Copyright Page
Table of Contents
Series Preface
Preface
Acknowledgements
Editor
Contributors
Abbreviations
1 MOLECULAR MECHANISMS OF BRAIN INSULIN SIGNALING
Interaction between Metabolism and Insulin
Insulin and Insulin Growth Factor 1 Receptor
Insulin Signaling Cascade in the Brain
Downstream Signaling from the Insulin and Insulin Growth Factor 1 Receptor
Insulin Signaling through the AKT Pathway
Extracellular Signal-Regulated Protein Kinases Isoforms
Negative Modulation of the Insulin Signaling Pathway
Genetic Mutations Associated with Insulin Resistance
Dephosphorylation of Proteins and Metabolites Involved in the Insulin Signaling Pathway
Inhibitory Phosphorylations of Proteins in the Insulin Signaling Pathway
Insulin and Insulin Growth Factor 1 Receptor
IR Expression in the Brain
Insulin Growth Factor 1 Receptor
Insulin and Insulin Growth Factor 1 Receptor Heterodimers
Insulin Receptor Substrate 1 Expression in the Brain
Insulin Receptor Substrate 2 Expression in the Brain
Insulin Receptor Substrate 4 Expression in the Brain
AKT Isoforms and Their Expression in the Brain
Extracellular Signal-Regulated Protein Kinases Isoforms and Their Expression in the Brain
Concluding Remarks
Acknowledgments
References
2 INSULI/IGF SIGNALING IN EARLY BRAIN DEVELOPMENT
Effects on the Developing Central Nervous System
First Steps in Central Nervous System Development: Neurulation
Expanding Central Nervous System Cells: Neurogenesis
Neuronal Survival and Development
Cellular Differentiation
Brain Region Specific Effects in Development
The Cortex
The Hippocampus
The Hypothalamus
Insulin Dependent Diseases and Brain Development Effects
Gestational Diabetes and Decreased Maternal Insulin Sensitivity
Malnutrition and Maternal Undernutrition
Polycystic Ovarian Syndrome (PCOS)
Concluding Remarks
References
3 INSULIN SIGNALING MODULATES NEURONAL METABOLISM
Introduction
Overview of Neuronal Metabolism and Bioenergetics
Insulin Regulates Neuronal Glucose Metabolism
Insulin Signaling and Astrocyte-Neuron Lactate Shuttling
Insulin Signaling and Ketone Body Metabolism in Neurons
Insulin and Glycogen Metabolism in Neurons
Insulin and Lipid Metabolism in Neurons
Insulin Signaling Contributes to Mitochondrial Function and Homeostasis in Neurons
Insulin Signaling Regulates Mitochondrial Bioenergetic Capacity
Insulin Signaling Regulates Mitochondrial Mass by Supporting Mitochondrial Biogenesis
Insulin Signaling Modulates Mitochondrial Stress Response Network
Potential Link between Impaired Insulin/IGF-1 Signaling and Mitochondrial Dysfunction in Neurodegenerative Diseases
Insulin Signaling Contributes to Intracellular Ca[sup(2+)] Homeostasis in Neurons
Concluding Remarks
Acknowledgements
References
4 REGULATION OF GLIAL FUNCTION BY INSULIN PEPTIDES
Introduction
Astroglia
Physiology
Pathology
Microglia
Physiology
Pathology
Oligodendroglia
Physiology
Pathology
Concluding Remarks
Acknowledgments
References
5 NEUROENDOCRINE INTERACTIONS IN THE CONTROL OF GLUCOSE- AND ENERGY HOMEOSTASIS
Regulation of Energy Homeostasis by Insulin
Regulation of Energy Homeostasis by Leptin
Leptin Homeostasis and Its Relevance for Insulin Action
The Glucoregulatory Role of Leptin
WNT/β-Catenin Signalling as an Integrator of Central Insulin and Leptin Action on Energy Homeostasis
Incretins and Energy Homeostasis
Concluding Remarks
Acknowledgements
References
6 HYPOTHALAMIC NEURONAL CIRCUITS ARE MODULATED BY INSULIN AND IMPACT METABOLISM
Introduction
The Hypothalamic Relevance of Insulin
How Insulin Targets the Hypothalamus
Insulin and the Hypothalamic Neuronal Circuits
The Arcuate Nucleus, Key Hypothalamic Region in the Insulin Signalling
Other Hypothalamic Circuits Modulated by Insulin
Non-Neuronal Insulin Targeting Places in the Hypothalamus
Astrocytes
Pericytes
Insulin Receptor Signalling in the Hypothalamus
The Canonical Insulin Signalling Pathway: PI3K-AKT Pathway
The PI3K K-ATP Downstream Pathway
mTOR/S6K Downstream Pathway
AMPK Downstream Pathway
The MAPK/ERK Pathway
Hypothalamic Insulin Signalling Impact Peripheral Metabolism
Neuronal Insulin Signalling Regulates Peripheral Metabolism
Brain Insulin Action in Hepatic Glucose Production and Triglyceride Export
Brain Insulin and White Adipose Tissue Metabolism
Brain Insulin and Brown Adipose Tissue Thermogenesis
Hypothalamic Insulin Resistance Impact Peripheral Metabolism
Proposed Mechanism by Which Brain Insulin Resistance Occurs
Brain Insulin Resistance and Its Metabolic Sequelae
Hypothalamic Insulin Resistance, a Maladaptive Response
Concluding Remarks
Acknowledgements
References
7 INSULIN AND BRAIN REWARD SYSTEMS
Introduction
Historical Perspective
Peripheral Insulin
The Insulin Receptor
Targeted Deletion of IRs in the CNS versus Peripheral Sites
Insulin in the Central Nervous System
Brain IRs and Insulin Signaling
Leptin
Ghrelin
Insulin, Dopamine, Feeding Behavior and the Hypothalamus
Central Insulin and Mood Disorders
Central Insulin as a Driver of Reward-Associated Behavior
The Reward System
Dopamine
Glutamate
GABA
The Mesolimbic Dopamine System and Central Insulin
Nucleus Accumbens
Mechanisms of Insulin Regulation of Dopamine Release
Insulin and Substance Use Disorders
Eating Disorders
Insulin and Parkinson's Disease
Concluding Remarks
Acknowledgements
References
8 THE IMPACT OF INSULIN ON BRAIN SEROTONERGIC SYSTEM: CONSEQUENCES ON DIABETESASSOCIATED MOOD DISORDERS
Introduction: The Comorbidity Diabetes-Depression
Overview of Brain Insulin Signaling
Effects of Brain Insulin on Emotionality
Evidence of the Impact of Insulin onto Serotonergic Neurotransmission
Overview of the Role of DRN 5-HT Neurons in Mood
Evidence of Insulin Action on the 5-HT Neurons
Effects of Insulin on 5-HT Sensitive Cells – Crosstalk between Insulin and Serotonin Signaling Pathways
Concluding Remarks
Acknowledgments
References
9 ORGAN CROSS-TALK REGULATES (BRAIN) INSULIN ACTION
Introduction
Adipose Tissue
Leptin
Adiponectin
Liver
Regulation of Fibroblast Growth Factor 21
Glucose Tolerance Is Improved by a Dietary Protein Restriction in Response to a High-Fat Diet
Dietary Amino Acid Restriction Protects from Type 2 Diabetes by FGF21 Secretion
Perspective
Insulin-Like Growth Factors
IGF1
IGF2
Gastrointestinal Tract and GLP-1
Concluding Remarks
Acknowledgments
References
10 INSULIN RESISTANCE AS A RISK FACTOR FOR ALZHEIMER'S DISEASE
Introduction
Peripheral Insulin Resistance as Risk Factor of Cognitive Alteration in Late Onset Alzheimer's Disease
Physiological Roles of Insulin in the Brain and in Late Onset Alzheimer's Disease
Late Onset Alzheimer's Disease and Brain Insulin Resistance
Molecular Pathways Involved in Central Insulin Resistance Associated with Late Onset Alzheimer's Disease Neurodegeneration
Amyloid as a Responsible of Brain Insulin Resistance in Late Onset Alzheimer's Disease
The Role of Tau in the Brain Insulin Resistance in the Late Onset Alzheimer's Disease
Apolipoprotein-ε4 and Insulin Resistance
PTP-1B as the Link between Brain Insulin Resistance Associated with Cognitive Loss and Late Onset Alzheimer's Disease
Neuroinflammation as a Link between Brain Insulin Resistance and Alzheimer's Disease
Glutamate Excitotoxicity as a Responsible for Brain Insulin Resistance
Mitochondrial Dysfunction Is Responsible for Brain Insulin Resistance
Mammalian Target of Rapamycin Signalling Modulates Insulin Resistance
Ceramides Regulate Insulin Resistance and Increase the Risk of Late Onset Alzheimer's Disease
Concluding Remarks
Acknowledgements
References
11 BRAIN INSULIN ACTION IN THE CONTROL OF METABOLISM IN HUMANS
Introduction
Investigating Central Insulin Action in Humans
Intranasal Insulin
Methods to Investigate Peripheral and Whole-Body Insulin Sensitivity
Glucose Challenge
Hyperinsulinemic-Euglycemic Glucose Clamp
Neuroimaging Methods to Quantify Central Insulin Action in Humans
Electroencephalography/Magnetoencephalography
Nuclear Tomographical Imaging Techniques
Functional Magnetic Resonance Imaging (fMRI)
Central Insulin Action- Evidence of EEG and MEG Studies
Regional Specific Central Insulin Action-Evidence of PET and fMRI Studies
Central Effects of Insulin Action on Behavior
Central Effects of Insulin Action on Systemic Metabolism
Definition of Brain Insulin Resistance in Humans
Concluding Remarks
Acknowledgements
References
12 IMPACT OF DIETARY AND EXERCISE INTERVENTIONS ON BRAIN INSULIN ACTION AND BRAIN FUNCTION
The Diet-Insulin-Brain Axis in Humans
Associations between General Dietary Factors and Neurological Outcomes
Epidemiological Impact of Lifestyle Factors on Obesity, Insulin Resistance and T2DM
Lifestyle and Dementia
Lifestyle and Depression
Metabolic Impact of Different Lifestyle Interventions on Obesity, Glycemia, and Insulin Resistance
Effects of Metabolically Beneficial Complex Lifestyle Changes on Cognition
Interventional Effects of Specific Lifestyle Components on Glycemic Metabolism and Cognition
Effects of Specific Dietary Interventions on Glycemic Metabolism and Mood
Concluding Remarks
References
13 PHARMACOLOGICAL AND SURGICAL INTERVENTIONS TO IMPROVE BRAIN INSULIN RESISTANCE
GLP-1 Agonist Treatment and Brain Insulin Resistance
Preclinical Evidence
Alzheimer's Disease Rodent Models
Alzheimer's Disease Cell Models
Parkinson's Disease (PD) Rodent Models
Clinical Evidence
AD Clinical Evidence
PD Clinical Evidence
Intranasal GLP-1 Application
Other Anti-Diabetic Drugs and Brain Insulin Resistance
Insulin
Peripheral Insulin
Intranasal Insulin
Insulin Sensitizers
Metformin
Peroxisome Proliferator-Activated Receptor Agonists (PPARs)
Incretin Analogues
Glucose-Dependent Insulinotropic Polypeptide (GIP) Analogues
Dual/Triple Agonists
Other Therapeutic Agents
Dipeptidyl-Peptidase 4 (DPP-4) Inhibitors
Sodium Dependent Glucose Co-Transporter 2 (SGLT-2) Inhibitors
Brain Insulin Sensitivity and Bariatric Surgery
Brain Insulin Sensitivity in Obesity
Brain Insulin Sensitivity, Conventional Weight Loss and Bariatric Surgery
Concluding Remarks
Literature
Index