Breaking News
December 11, 2018 - Cartilage tissue engineering brings good news for patients with cartilage defects
December 11, 2018 - Novel 3D printing workflow helps predict leaky heart valves
December 11, 2018 - Are caries linked to political regime?
December 11, 2018 - Leader in Diabetes Clinical Trials Wins Naomi Berrie Award
December 11, 2018 - Scientists discover cellular mechanism that triggers pneumonia in humans
December 11, 2018 - Increasing mental health problems related to drug use in over 55’s
December 11, 2018 - High-intensity interval exercise could help combat cognitive dysfunction in obese people
December 11, 2018 - Annual flu shot can save lives of heart failure patients
December 11, 2018 - Researchers compare health outcomes for VA and non-VA hospitals
December 11, 2018 - Recommendations Developed for Psoriatic Arthritis Treatment
December 11, 2018 - Genetic analysis links obesity with diabetes, coronary artery disease
December 11, 2018 - Study shows that having genetic information can affect how the body responds
December 11, 2018 - UNAIDS Report: 9 Million Are Likely HIV Positive And Don't Know It
December 11, 2018 - Lund University researchers succeed in obtaining dendritic cells by direct reprogramming
December 11, 2018 - Breast tumors recruit bone marrow cells to boost their growth, study reveals
December 11, 2018 - Updated breast cancer screening guideline highlights importance of shared decision-making
December 11, 2018 - EHR-related stress associated with physician burnout
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Researchers explore how glial cells develop in the brain from neural precursor cells
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Experts address sleep disorders following traumatic brain injury
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
December 10, 2018 - Hazelnuts improve micronutrient levels in older adults
December 9, 2018 - History of Partner Violence Tied to Menopause Symptoms
December 9, 2018 - Clean Up Safely After a Disaster|Natural Disasters and Severe Weather
December 9, 2018 - Drug wholesalers drove fentanyl’s deadly rise, report concludes
December 9, 2018 - Deprescribing could help manage polypharmacy in older adults
December 9, 2018 - Retraction of article “Joy of cooking too much” from journal
December 9, 2018 - FDA Warns of Rare Stroke Risk With MS Drug Lemtrada (Alemtuzumab)
Research reveals link between immunity, diabetes

Research reveals link between immunity, diabetes

image_pdfDownload PDFimage_print
Credit: CC0 Public Domain

When it comes to diet-induced obesity, your immune system is not always your friend.

Adipose (fatty) tissue is infiltrated by white blood cells that have been linked to the development of inflammation, insulin resistance and type 2 diabetes. How this happens is complicated and under intense investigation by researchers around the world.

Now, from a study in mice fed a high-fat diet, Vanderbilt researchers report that a type of immune cell called the CD8+ T cell is activated in fatty tissue by isolevuglandins (isoLGs), chemical products of fatty acid oxidation.

Part of the body’s immune defense system, CD8+ cells attack bacteria, viruses and unhealthy cells including cancer cells. But in fat they also contribute to inflammation, which is thought to block insulin’s ability to remove glucose from the blood. Insulin “resistance,” in turn, can lead to type 2 diabetes.

“This study is important because it enhances our understanding of the immune system and how it contributes to insulin resistance in the setting of obesity,” said the paper’s first author, Wyatt McDonnell, a graduate student in the Department of Pathology, Microbiology and Immunology at Vanderbilt University School of Medicine.

The findings, reported last week in the journal Diabetes, suggest that drugs could be developed to prevent or reverse insulin resistance by targeting isoLGs or CD8+ cells in fatty tissue, added the paper’s corresponding author, Arion Kennedy, Ph.D., a former Vanderbilt faculty member now at North Carolina State University in Raleigh.

The current study was made possible by Kennedy, co-author Alyssa Hasty, Ph.D., and colleagues who showed in earlier work that CD8+ cells can be isolated from adipose tissue. Hasty is the Cornelius Vanderbilt Chair and professor in the Department of Molecular Physiology and Biophysics.

CD8+ T cells contain unique and highly variable “barcodes” that enable them to recognize their targets. Using sophisticated cell sorting and gene-sequencing technology provided through the Vanderbilt Flow Cytometry Shared Resource and VANTAGE (Vanderbilt Technologies for Advanced Genomics), the researchers sequenced the barcode of each CD8+ cell isolated from fat.

This part of the research and the computational analysis was led by McDonnell, who worked with co-author and VANTAGE Scientific Director Simon Mallal, MBBS, the Major E.B. Stahlman Professor of Infectious Diseases and Inflammation.

The researchers found that the barcode changed under conditions of diet-induced obesity. “This led us to discover that isoLGs—a type of modified protein made by cells experiencing stress and injury from oxygen free radicals—are elevated in the fat,” McDonnell said, and that CD8+ cells are activated by them.

“This study is the first to show that the accumulation of CD8+ cells in fat during obesity is not a random process,” said co-author John Koethe, MD, MSCI, assistant professor of Medicine at Vanderbilt.

Koethe said the findings are relevant for patients with HIV disease who also have elevated levels of CD8+ cells in fat and are at high risk of developing diabetes. Last year he received a five-year, $3.6 million grant from the National Institutes of Health (NIH) to better understand and find a solution to this problem.

Studies conducted by co-author Annet Kirabo, Ph.D., MSc, assistant professor in the Division of Clinical Pharmacology, and colleagues also have linked IsoLGs to the development of high blood pressure and vascular disease.

This suggests a conserved pathway by which the immune system “misbehaves” in hypertension, diabetes and obesity. “It also means we could potentially intervene in these settings by quieting down the immune system or by lowering the oxidative stress on cells in the fat,” McDonnell said.


Explore further:
Gamma-Delta T cells may play a role in insulin resistance and type 2 diabetes

More information:
Wyatt J. McDonnell et al. High CD8 T Cell Receptor Clonality and Altered CDR3 Properties are Associated with Elevated Isolevuglandins in Adipose Tissue During Diet-Induced Obesity, Diabetes (2018). DOI: 10.2337/db18-0040

Journal reference:
Diabetes

Provided by:
Vanderbilt University

Tagged with:

About author

Related Articles