Abstract
Alzheimer’s disease (AD) is the most common form of dementia worldwide. Type 2 diabetes (T2D) has been implicated as a risk factor for AD. Since T2D is a peripheral inflammatory condition, and AD brains exhibit exacerbated neuroinflammation, we hypothesized that inflammatory mechanisms could contribute to the observed link between T2D and AD. Abnormal peripheral and brain insulin concentrations have been reported in both T2D and AD. The neurotrophic role of insulin has been described; however, this hormone can also regulate inflammatory responses in the periphery. Therefore we used in vitro human cell culture systems to elucidate the possible effects of insulin on neuroinflammation. We show that human astrocytes and microglia express both isoforms of the insulin receptor as well as the insulin-like growth factor (IGF)-1 receptor. They also express insulin receptor substrate (IRS)-1 and IRS-2, which are required for propagation of insulin/IGF- 1 signaling. We show that at low nanomolar concentrations, insulin could be pro-inflammatory by upregulating secretion of interleukin (IL)-6 and IL-8 from stimulated human astrocytes and secretion of IL-8 from stimulated human microglia. This effect dissipates at higher insulin concentrations. In contrast, insulin at a broader concentration range (10 pM – 1 μM) reduces the toxicity of stimulated human microglia and THP-1 monocytic cells towards SH-SY5Y neuronal cells. These data show that insulin may regulate the inflammatory status of glial cells by modulating their select functions, which in turn can influence the survival of neurons contributing to the observed link between T2D and AD.
Keywords: Alzheimer’s disease, astrocytes, cytokines, IGF-1, microglia, neurodegeneration, neurotoxicity, type 2 diabetes.
Current Alzheimer Research
Title:Insulin Modulates In Vitro Secretion of Cytokines and Cytotoxins by Human Glial Cells
Volume: 12 Issue: 7
Author(s): Lindsay J. Spielman, Manpreet Bahniwal, Jonathan P. Little, Douglas G. Walker and Andis Klegeris
Affiliation:
Keywords: Alzheimer’s disease, astrocytes, cytokines, IGF-1, microglia, neurodegeneration, neurotoxicity, type 2 diabetes.
Abstract: Alzheimer’s disease (AD) is the most common form of dementia worldwide. Type 2 diabetes (T2D) has been implicated as a risk factor for AD. Since T2D is a peripheral inflammatory condition, and AD brains exhibit exacerbated neuroinflammation, we hypothesized that inflammatory mechanisms could contribute to the observed link between T2D and AD. Abnormal peripheral and brain insulin concentrations have been reported in both T2D and AD. The neurotrophic role of insulin has been described; however, this hormone can also regulate inflammatory responses in the periphery. Therefore we used in vitro human cell culture systems to elucidate the possible effects of insulin on neuroinflammation. We show that human astrocytes and microglia express both isoforms of the insulin receptor as well as the insulin-like growth factor (IGF)-1 receptor. They also express insulin receptor substrate (IRS)-1 and IRS-2, which are required for propagation of insulin/IGF- 1 signaling. We show that at low nanomolar concentrations, insulin could be pro-inflammatory by upregulating secretion of interleukin (IL)-6 and IL-8 from stimulated human astrocytes and secretion of IL-8 from stimulated human microglia. This effect dissipates at higher insulin concentrations. In contrast, insulin at a broader concentration range (10 pM – 1 μM) reduces the toxicity of stimulated human microglia and THP-1 monocytic cells towards SH-SY5Y neuronal cells. These data show that insulin may regulate the inflammatory status of glial cells by modulating their select functions, which in turn can influence the survival of neurons contributing to the observed link between T2D and AD.
Export Options
About this article
Cite this article as:
Spielman J. Lindsay, Bahniwal Manpreet, Little P. Jonathan, Walker G. Douglas and Klegeris Andis, Insulin Modulates In Vitro Secretion of Cytokines and Cytotoxins by Human Glial Cells, Current Alzheimer Research 2015; 12 (7) . https://dx.doi.org/10.2174/1567205012666150710104428
DOI https://dx.doi.org/10.2174/1567205012666150710104428 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Cancer Kinases and its Novel Inhibitors: Past, Present and Future Challenges
Current Drug Targets Conformational Diseases and Structure-Toxicity Relationships: Lessons from Prion-Derived Peptides
Current Protein & Peptide Science Fragment Based Strategies for Discovery of Novel HIV-1 Reverse Transcriptase and Integrase Inhibitors
Current Topics in Medicinal Chemistry Nerve Growth Factor Receptors and Signaling in Breast Cancer
Current Cancer Drug Targets Syntheses and Evaluation of Asymmetric Curcumin Analogues as Potential Multifunctional Agents for the Treatment of Alzheimer’s Disease
Current Alzheimer Research A Closer Look to Polyesters: Properties, Synthesis, Characterization, and Particle Drug Delivery Applications
Nanoscience & Nanotechnology-Asia Neuropeptide FF Inhibits LPS-Mediated Osteoclast Differentiation of RAW264.7 Cells
Protein & Peptide Letters Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids
Current Medicinal Chemistry Potential Role of Calcium/Calmodulin-dependent Protein Kinase II to Angiogenesis Mediated Pathological Changes Seen in Osteoarthritis
Current Angiogenesis (Discontinued) Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise
Current Pharmaceutical Design An Overview of the Chemistry and Pharmacological Potentials of Furanones Skeletons
Current Organic Chemistry Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects
Current Medicinal Chemistry Voltage Gated ion Channels: Targets for Anticonvulsant Drugs
Current Topics in Medicinal Chemistry Peroxisome Proliferator Activated Receptor-Gamma Ligands as Potent Antineoplastic Agents
Current Medicinal Chemistry - Anti-Cancer Agents Targeting Chemokine Receptor CXCR4 for Treatment of HIV-1 Infection, Tumor Progression, and Metastasis
Current Topics in Medicinal Chemistry Microdialysis: A Technique for Pharmacokinetic-Pharmacodynamic Studies of Oncological Drugs
Current Pharmaceutical Biotechnology Synthetic and Biological Aspects of Thiadiazoles and their Condensed Derivatives: An Overview
Current Topics in Medicinal Chemistry Role of Netrin-1 Beyond the Brain: From Biomarker of Tissue Injury to Therapy for Inflammatory Diseases
Recent Patents on Biomarkers Regulators of G Protein Signaling: Potential Drug Targets for Controlling Cardiovascular and Immune Function
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Grape Seed Proanthocyanidins Protect N2a Cells against Ischemic Injury via Endoplasmic Reticulum Stress and Mitochondrial-associated Pathways
CNS & Neurological Disorders - Drug Targets