The key participants in a molecular pathway that holds therapeutic promise for reducing the severity of type 2 diabetes has been identified by scientists.
Their study looked at the role of adenosine, an immune system signaling molecule, in triggering inflammation, which significantly contributes to insulin resistance.nsulin resistance keeps the body from properly handling sugar and is one of the key factors underlying type 2 diabetes.
"Several previous studies have shown that if you block adenosine signaling, insulin resistance is diminished. However, it wasn't known exactly how the process worked or which cells were directly involved," said senior author and La Jolla Institute scientist Joel Linden.
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 Linden.
The study led by Linden involved scientists from Pennsylvania State University, the University of Virginia, the La Jolla Institute for Allergy and Immunology and Clinical Data, Inc.
In type 2 diabetes, Linden explained, the ability of insulin to stimulate glucose uptake by the tissues is reduced, an occurrence known as insulin resistance.
"We believe, as do many scientists, that insulin resistance involves macrophages, which are cells of the body that contribute to inflammation," Linden 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," he said.
By using an adenosine receptor blocker, the team prevented the adenosine from activating the macrophages, according to Linden.
As a result the tissues began to better respond to insulin, which reduces blood sugar levels in diabetic animals.
The findings were published in the February issue of the scientific journal Diabetes.