Navigation Links
La Jolla Institute-led team illuminates cell pathway key to insulin resistance in Type 2 diabetes
Date:2/24/2011

SAN DIEGO (February 24, 2011) A research team, led by La Jolla Institute scientist Joel Linden, Ph.D., has shed new light on the problem of insulin resistance, and identified the key participants in a molecular pathway that holds therapeutic promise for reducing the severity of type 2 diabetes.

The researchers looked at the role of adenosine, an immune system signaling molecule, in triggering inflammation, which significantly contributes to insulin resistance. Insulin resistance keeps the body from properly handling sugar and is one of the key factors underlying type 2 diabetes. Diabetes now affects nearly 26 million Americans and is the seventh leading cause of death in the U.S., according to the Centers for Disease Control.

"Several previous studies have shown that if you block adenosine signaling, insulin resistance is diminished," said Dr. Linden. "However, it wasn't known exactly how the process worked or which cells were directly involved."

Dr. Linden's team identified the primary cellular players in the adenosine-fueled inflammation cascade that contributes to insulin resistance. Their study, in animal models, also tested the effectiveness of a recently synthesized adenosine receptor blocker. "We found that if you use this molecule to selectively block one of the adenosine receptors, insulin resistance is decreased and diabetes gets better," said Dr. Linden, one of the world's leading authorities on adenosine.

Eugene Barrett, Ph.D., a past president of the American Diabetes Association, praised the study's findings as important. "There is a great need for new approaches to lessen the disease burden caused by insulin resistance," said Dr. Barrett, a professor of medicine and director of the University of Virginia's Diabetes Center, which was not involved in the study. "The work of Dr. Linden and his collaborators opens a new avenue to explore with possibly important therapeutic implications."

The findings were published in a paper entitled "Links Between Insulin Resistance, Adenosine A2B Receptors, and Inflammatory Markers in Mice and Humans" in the February issue of the scientific journal Diabetes. Dr. Linden was senior author on the study, which involved scientists from Pennsylvania State University, the University of Virginia, the La Jolla Institute for Allergy & Immunology and Clinical Data, Inc., a pharmaceutical company examining possible therapeutic applications targeting adenosine receptors. Robert A. Figler, Ph.D., of Clinical Data Inc. was first author on the paper.

"Our study clarifies the molecular steps triggered by adenosine, which leads to inflammation linked not only to type 2 diabetes but to other inflammatory diseases," Dr. Figler said. Clinical Data has an ongoing development program in A2B receptor antagonists, he added, and is pursuing the therapeutic potential of these agents in diabetes as well as asthma. Clinical Data plans to soon begin a clinical trial for patients with asthma.

In type 2 diabetes, Dr. Linden explained, the ability of insulin to stimulate glucose uptake by the tissues is reduced, an occurrence known as insulin resistance. "Insulin's job is to move glucose out of the blood stream and into other body tissues, where it can be used," he said. "If insulin can't do its job because the body's tissues aren't responding to it sufficiently, then you end up with a buildup of sugar in the blood."

"So we asked ourselves the question," Dr. Linden continued, 'why don't the tissues respond?'"

Recently, said Dr. Linden, the scientific community has learned that type 2 diabetes is associated with chronic low-grade inflammation. "We believe, as do many scientists, that insulin resistance involves macrophages, which are cells of the body that contribute to inflammation," he explained. "We discovered that adenosine stimulates macrophages. The macrophages then release chemicals called cytokines, which are molecules that rev up the immune system. We believe it is the cytokines that cause tissues to become less sensitive to insulin."

By using an adenosine receptor blocker, the team prevented the adenosine from activating the macrophages, said Dr. Linden. "So the downstream effect of releasing cytokines does not occur." The result? The tissues began to better respond to insulin, which reduces blood sugar levels in diabetic animals.

While sensitivity to insulin was significantly improved, Dr. Linden said insulin resistance was not completely reversed. "We will be studying this further to better understand the details of insulin resistance," he said.


'/>"/>

Contact: Bonnie Ward
contact@liai.org
619-303-3160
La Jolla Institute for Allergy and Immunology
Source:Eurekalert

Related biology news :

1. La Jolla Institute signs exclusive license agreement with Medimmune on major asthma discovery
2. La Jolla Institute discovers novel tumor suppressor
3. Visionary concept earns La Jolla Institute scientist prestigious NIH Pioneer Award
4. La Jolla Institute scientist leads team which discovers important new player in diabetes onset
5. La Jolla Institute scientist Klaus Ley receives Malpighi award
6. La Jolla Institute validates Type 1 diabetes computer models predictive success through lab testing
7. Discovery of stem cell illuminates human brain evolution, points to therapies
8. Tiny laser light show illuminates quantum computing
9. New imaging advance illuminates immune response in breathing lung
10. Breast cancer treatment resistance linked to signaling pathway
11. Barcelona Declaration 2008: Challenges and Pathways to Earth Sustainability
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... WearablesResearch.com , a brand of Troubadour Research & ... Q1 wave of its quarterly wearables survey. A particular ... a program where they would receive discounts for sharing ... "We were surprised to see that so many ... CEO of Troubadour Research, "primarily because there are segments ...
(Date:4/28/2016)... , April 28, 2016 First quarter ... (139.9), up 966% compared with the first quarter of 2015 ... totaled SEK 589.1 M (loss: 18.8) and the operating margin was ... (loss: 0.32) Cash flow from operations was SEK 249.9 ... 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. The ...
(Date:4/15/2016)... 2016  A new partnership announced today will ... decisions in a fraction of the time it ... high-value life insurance policies to consumers without requiring ... Force Diagnostics, rapid testing (A1C, Cotinine and HIV) ... pressure, weight, pulse, BMI, and activity data) available ...
Breaking Biology News(10 mins):
(Date:5/27/2016)... and READING, England ... Indegene ( http://www.indegene.com ), ein ... Lösungen für die Life-Science-Branche, Pharmaunternehmen und Gesundheitsorganisationen, ... weltweiter Anbieter von innovativen wissenschaftlichen Support-Services für ... Starts von IntraScience heute den Ausbau ihrer ...
(Date:5/26/2016)... , May 26, 2016 Despite ... see value in this space. Today,s pre-market research on ActiveWallSt.com ... Radius Health Inc. (NASDAQ: RDUS ), Cerus Corp. ... ARWR ), and Five Prime Therapeutics Inc. (NASDAQ: ... technical briefings at: http://www.activewallst.com/ ...
(Date:5/25/2016)... ... May 25, 2016 , ... Thailand’s Board of Investment’s ... in San Francisco. Located at booth number 7301, representatives from the Thai Government, ... discuss the Thai biotechnology and life sciences sector. , Deputy Secretary General ...
(Date:5/25/2016)... ... May 25, 2016 , ... WEDI, the nation’s leading ... today announced that Charles W. Stellar has been named by the WEDI Board of ... January 2016. As an executive leader with more than 35 years of experience in ...
Breaking Biology Technology: