Endocannabinoids trigger inflammation that leads to diabetes

(Medical Xpress)—Researchers at the National Institutes of Health have clarified in rodent and test tube experiments the role that inflammation plays in type 2 diabetes, and revealed a possible molecular target for treating the disease. The researchers say some natural messenger chemicals in the body are involved in an inflammatory chain that can kill cells in the pancreas, which produces insulin.

A report of the finding appears online in Nature Medicine.

"This study is a significant milestone in an ongoing exploration of the 's role in the metabolic ," says Kenneth R. Warren, Ph.D., acting director of NIH's National Institute on Alcohol Abuse and Alcoholism (NIAAA), which led the study.

Endocannabinoids are natural messengers in the body that help regulate many biological functions. They are chemically similar to the active compound in marijuana. Recent studies have tied to the metabolic problems that lead to diabetes. Researchers also have recognized that inflammation appears to play an important role in the pathology of diabetes.

"The identities of the molecular and cellular actors in the inflammatory processes that underlie type 2 diabetes have remained elusive," explains senior author and NIAAA scientific director George Kunos, M.D., Ph.D. "Our study connects endocannabinoids to an inflammatory cascade leading to the loss of in the pancreas, which is a hallmark of type 2 diabetes."

Working with a strain of genetically obese rats that serve as a model for human type 2 diabetes, Dr. Kunos and his colleagues used a combination of pharmacological and to show that endocannabinoids trigger receptors on macrophages in the pancreas. Macrophages are , present in all tissues that rid the body of cellular debris and pathogens.

"Like various other , such as the liver, skeletal muscles, pancreas, and fatty tissue, macrophages have receptors for endocannabinoids," explains Dr. Kunos.

The researchers demonstrated that endocannabinoid activation of macrophages in the pancreas leads to activation of a protein complex within macrophages called the Nlrp3 inflammasome. The inflammasome, in turn, releases molecules that cause the death of pancreatic beta cells and the progression of type 2 diabetes in the rats.

"When we treated the rats with compounds that deplete macrophages or block all peripheral cannabinoid receptors, inflammasome activation and type 2 diabetes progression was slowed," noted Dr. Kunos.

In , the researchers showed that macrophages from humans and mice produced the same inflammasome response when they were incubated with endocannabinoids. However, mouse macrophages that were genetically altered to lack cannabinoid receptors or inflammasomes generated no such response.

Most notably, the researchers showed that by selectively blocking the expression of cannabinoid receptors on macrophages, they could protect and restore beta cell function in the genetically obese rats, which delayed the development and reduced the severity of their diabetes.

The authors conclude that the findings point to a key role in type 2 diabetes for endocannabinoid-induced inflammasome activation in macrophages, and identify cannabinoid receptors on macrophages as a new therapeutic target.

"To understand type 2 diabetes, a public health threat that affects young and old alike, we need to consider all the factors at play," said Monica Skarulis, M.D., staff clinician at National Institute of Diabetes and Digestive and Kidney Diseases and co-author. "We hope that what we've learned from this research will help us develop new strategies to prevent and treat the condition."

More information: Jourdan, T, et al. Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes. Nature Medicine, 2013 August 18.

Related Stories

New Compound Improves Obesity-Related Health Complications

Jul 26, 2010

 (PhysOrg.com) -- An experimental compound appears to improve metabolic abnormalities associated with obesity, according to a preliminary study led by researchers at the National Institutes of Health, A report of the study, ...

Researchers prevent mice from developing diabetes

Jun 29, 2012

(Medical Xpress) -- Swedish research group headed at Karolinska Institutet has been able to prevent onset of Type 1 diabetes in mice that are genetically susceptible to the disease. Through injection of specifically ...

Team discovers potential new way to treat anxiety

Aug 04, 2013

Chemically modified inhibitors of the COX-2 enzyme relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects, Vanderbilt University scientists will report ...

Recommended for you

New technology allows hair to reflect almost any color

Jul 25, 2014

What if you could alter your hair to reflect any color in the spectrum? What if you could use a flatiron to press a pattern into your new hair color? Those are possibilities suggested by researchers from ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

dr k ramakrishnan
not rated yet Aug 20, 2013
What is endocannabiates? Is there any drug or other natural materials available?