Abstract
Neuroinflammation has emerged as an important cause of cognitive decline during aging and in Alzheimer’s disease (AD). Chronic low-grade inflammation is observed in obesity and diabetes, which are important risk factors for AD. Therefore, we examined the markers of inflammation in the brain hippocampal samples of Zucker diabetic fatty (ZDF) rats. Pathway-specific gene expression profiling revealed significant increases in the expression of oxidative stress and inflammatory genes. Western blot analysis further showed the activation of NF-kB, defective CREB phosphorylation, and decreases in the levels of neuroprotective CREB target proteins, including Bcl-2, BDNF, and BIRC3 in the diabetic rat brain samples, all of which are related to AD pathology. As therapies based on glucagon-like peptide-1 (GLP-1) are effective in controlling blood glucose levels in type 2 diabetic patients, we tested the in vivo actions of GLP-1 in the diabetic brain by a 10-wk treatment of ZDF rats with alogliptin, an inhibitor of dipeptidyl peptidase. Alogliptin increased the circulating levels of GLP-1 by 125% and decreased blood glucose in diabetic rats by 59%. Normalization of defective signaling to CREB in the hippocampal samples of treated diabetic rats resulted in the increased expression of CREB targets. Dual actions of GLP-1 in the pancreatic beta cells and in the brain suggest that incretin therapies may reduce cognitive decline in the aging diabetic patients and also have the potential to be used in treating Alzheimer’s patients.
Keywords: Brain, cognitive function and Alzheimer’s disease, CREB, Diabetes, dipeptidyl peptidase-4, Glucagon-like peptide- 1, hippocampus, inflammation, insulin, oxidative stress.
Current Alzheimer Research
Title:Glucagon-Like Peptide-1-Mediated Modulation of Inflammatory Pathways in the Diabetic Brain: Relevance to Alzheimer’s Disease
Volume: 13 Issue: 12
Author(s): LiMei Qin, Thomas Chong, Richard Rodriguez and Subbiah Pugazhenthi
Affiliation:
Keywords: Brain, cognitive function and Alzheimer’s disease, CREB, Diabetes, dipeptidyl peptidase-4, Glucagon-like peptide- 1, hippocampus, inflammation, insulin, oxidative stress.
Abstract: Neuroinflammation has emerged as an important cause of cognitive decline during aging and in Alzheimer’s disease (AD). Chronic low-grade inflammation is observed in obesity and diabetes, which are important risk factors for AD. Therefore, we examined the markers of inflammation in the brain hippocampal samples of Zucker diabetic fatty (ZDF) rats. Pathway-specific gene expression profiling revealed significant increases in the expression of oxidative stress and inflammatory genes. Western blot analysis further showed the activation of NF-kB, defective CREB phosphorylation, and decreases in the levels of neuroprotective CREB target proteins, including Bcl-2, BDNF, and BIRC3 in the diabetic rat brain samples, all of which are related to AD pathology. As therapies based on glucagon-like peptide-1 (GLP-1) are effective in controlling blood glucose levels in type 2 diabetic patients, we tested the in vivo actions of GLP-1 in the diabetic brain by a 10-wk treatment of ZDF rats with alogliptin, an inhibitor of dipeptidyl peptidase. Alogliptin increased the circulating levels of GLP-1 by 125% and decreased blood glucose in diabetic rats by 59%. Normalization of defective signaling to CREB in the hippocampal samples of treated diabetic rats resulted in the increased expression of CREB targets. Dual actions of GLP-1 in the pancreatic beta cells and in the brain suggest that incretin therapies may reduce cognitive decline in the aging diabetic patients and also have the potential to be used in treating Alzheimer’s patients.
Export Options
About this article
Cite this article as:
Qin LiMei, Chong Thomas, Rodriguez Richard and Pugazhenthi Subbiah, Glucagon-Like Peptide-1-Mediated Modulation of Inflammatory Pathways in the Diabetic Brain: Relevance to Alzheimer’s Disease, Current Alzheimer Research 2016; 13 (12) . https://dx.doi.org/10.2174/1567205013666160401114751
DOI https://dx.doi.org/10.2174/1567205013666160401114751 |
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
- 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
-
18F-FDG-PET/CT in Patients Affected by Differentiated Thyroid Carcinoma with Positive Thyroglobulin Level and Negative 131I Whole Body Scan. It's Value Confirmed by a Bicentric Experience
Current Radiopharmaceuticals Cystatin C: An Emerging Biomarker in Cardiovascular Disease
Current Topics in Medicinal Chemistry The Emergence of Non-coding RNAs as Versatile and Efficient Therapeutic Tools
Current Gene Therapy Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
Current Diabetes Reviews Angiogenesis Markers in Gynecological Tumors and Patents for Anti- Angiogenic Approach: Review
Recent Patents on Anti-Cancer Drug Discovery CXCL12-CXCR4 Axis in Angiogenesis, Metastasis and Stem Cell Mobilization
Current Pharmaceutical Design Bile Acids and Derivatives, Their Nuclear Receptors FXR, PXR and Ligands: Role in Health and Disease and Their Therapeutic Potential
Anti-Cancer Agents in Medicinal Chemistry The mTOR Signaling Network: Insights from Its Role During Embryonic Development
Current Medicinal Chemistry Ghrelin: A Gastric Peptide that Regulates Hypothalamic Control of Feeding
Current Medicinal Chemistry - Central Nervous System Agents Patent Selections:
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery From Na+/K+-ATPase and Cardiac Glycosides to Cytotoxicity and Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Prediction and Analysis of Hepatocellular Carcinoma Related Genes Using Gene Ontology and KEGG
Current Bioinformatics Safety of Nanoparticles in Medicine
Current Drug Targets Nutritional Control, Gene Regulation, and Transformation of Vascular Smooth Muscle Cells in Atherosclerosis
Cardiovascular & Hematological Disorders-Drug Targets DNMT Inhibitors in Cancer, Current Treatments and Future Promising Approach: Inhibition of Specific DNMT-Including Complexes
Epigenetic Diagnosis & Therapy (Discontinued) Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes
Current Gene Therapy Anti-tumor Drug Targets Analysis: Current Insight and Future Prospect
Current Drug Targets Influence of the Bystander Effect on HSV-tk / GCV Gene Therapy. A Review.
Current Gene Therapy Radiolabeled Peptides and Proteins in Cancer Therapy
Protein & Peptide Letters Zinc, Metallothioneins and Longevity: Interrelationships with Niacin and Selenium
Current Pharmaceutical Design