Tagged: Type 2 Diabetes

BUSM Study Reveals B cells as Therapeutic Targets to Alter Obesity-Associated Inflammation and Type 2 Diabetes

March 20th, 2013 in 2013, News Releases, School of Medicine 0 comments

FOR IMMEDIATE RELEASE, March 12, 2013,
Jenny Eriksen Leary, 617-638-6841, jenny.eriksen@bmc.org

(Boston) – New research from Boston University School of Medicine (BUSM) reveals that B cells regulate obesity-associated inflammation and type 2 diabetes through two specific mechanisms. The study, published in the Proceedings of the National Academy of Sciences, indicates the importance of continuing to explore B cells as a therapeutic target to treat these diseases. Barbara Nikolajczyk, PhD, associate professor of microbiology at BUSM, is the study’s senior author.

The incidence of diabetes continues to rise at alarming rates. According to the National Institute of Diabetes and Digestive and Kidney Diseases, the disease now affects approximately 25.8 million Americans. In 2007, the National Institutes of Health estimated that the direct and indirect costs of diabetes were a staggering $174 billion.

Type 2 diabetes, which is a common result of obesity, occurs when the body produces insulin but cannot use it properly (insulin resistance) or the body does not produce enough insulin. The body needs insulin to absorb glucose and generate energy. If the body does not produce and respond to insulin appropriately, it can, over time, lead to various complications such as cardiovascular disease, nerve damage, kidney disease and blindness.

Previous research has shown that B cells, which are white blood cells of the immune system, promote inflammation and can lead to the development of type 2 diabetes, but the mechanisms underlying B cell function were unclear.

The results of this study shed light on that question and indicate that B cells secrete a pro-inflammatory ratio of proteins called cytokines, which directly promote the insulin resistance that characterizes type 2 diabetes. The researchers also demonstrated that B cells directly regulate inflammatory T cells, an immune cell type known to cause insulin resistance in animal models of disease.

“Now that we have identified the specific mechanisms by which B cells promote inflammation, we can help develop novel, targeted approaches to treat type 2 diabetes,” said Nikolajczyk. “Our study supports the continued exploration of FDA-approved B cell depletion drugs, which are known to be generally safe and effective, as novel agents to prevent obesity-associated inflammation and type 2 diabetes.”

Research included in this study was supported in part by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under grant award numbers R21DK089270 and R56DK096525 (PI: Nikolajczyk) and R56DK090455 (PI: Gerald Denis); the NIDDK’s Boston Area Diabetes Endocrinology Research Center Pilot Program and the Boston Nutrition Obesity Research Center under grant award number DK046200; the NIH’s National Institute of Dental and Craniofacial Research under grant award number 5R21DE021154 (PI: Nikolajczyk); the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Immunology Training Program under grant award number AI007309; the NIH’s National Heart, Lung, and Blood Institute’s Hematology Training Program under grant award number HL007501; and the Evans Center for Interdisciplinary Biomedical Research at BUSM (PI: Nikolajczyk and Denis).

 

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BUSM study identifies Adenosine Receptor’s role in regulating high fat diet-induced obesity and Type 2 Diabetes

July 26th, 2012 in Health & Medicine, News Releases, School of Medicine 0 comments

Contact: Jenny Eriksen Leary, 617-638-6841, jenny.eriksen@bmc.org

(Boston) – A recent study led by Boston University School of Medicine (BUSM) demonstrates that the A2b-type adenosine receptor, A2bAR, plays a significant role in the regulation of high fat, high cholesterol diet-induced symptoms of type 2 diabetes. The findings, which are published online in PLoS ONE, also identify A2bAR as a potential target for the treatment of type 2 diabetes.

Katya Ravid, DSc/PhD, professor of medicine and biochemistry and director of the Evans Center for Interdisciplinary Biomedical Research at BUSM, led this study. Colleagues from Ravid’s lab who collaborated on this research include Hillary Johnston-Cox, BSc (MD/PhD, 2014) and Milka Koupenova-Zamor, PhD. Noyan Gokce, MD, associate professor of medicine at BUSM, and Melissa Farb, PhD, a postdoctoral fellow at BUSM, also collaborated on the study.

Diets that are high in fat and cholesterol induce changes in how the body regulates blood glucose levels. Exercise induces an increased production adenosine, a metabolite produced naturally by cells. A2bAR, a naturally occurring protein receptor found in the cell membrane, is activated by adenosine. This receptor is known to play an important role in regulating inflammation, which is associated with type 2 diabetes and obesity.

To examine the association of A2bAR activation with a diet high in fat and cholesterol, the researchers used an experimental model that lacked A2bAR and compared the results with a control group. When the experimental model group was given a diet high in fat and cholesterol, there was an increase in the development of obesity and signs of type 2 diabetes. The signs demonstrated in the study included elevated blood glucose levels and increased in insulin levels. When the control group was given the same diet, however, the levels of A2bAR increased, resulting in decreased insulin and glucose levels and obesity.

A novel link also was identified between the expression of A2bAR, insulin receptor substrate 2 (IRS-2) and insulin signaling. The results showed that the level of IRS-2, a protein that has previously been shown to mediate the effect of insulin, was impaired in tissues of the experimental model lacking A2bAR, causing higher concentrations of blood glucose. When A2bAR was activated in the control group using a pharmacologic agent with a diet high in fat and cholesterol, the level of IRS-2 was upregulated, lowering blood glucose.

“The pharmacologic activation of A2bAR demonstrated its newly identified role in signaling down to regulate the levels of IRS-2, which then improved the signs of high fat diet-induced type 2 diabetes,” said Ravid.

The prevalence of type 2 diabetes and obesity continues to increase in developed countries and both factors are known to contribute to the development of cardiovascular disease. According to the World Health Organization, 346 million people worldwide have diabetes and 90 percent of those people have type 2 diabetes.

To correlate these results in humans, the researchers then examined fat tissue samples from obese individuals. The results showed that A2bAR expression is high in fat from obese individuals, marked by inflammation, compared to lean ones, and is strongly correlated with IRS-2 expression.

“Our study suggests the important role of A2bAR in maintaining the level of IRS-2, a regulator of glucose and insulin homeostasis,” added Ravid.

This study was funded in part by the National Heart, Lung and Blood Institute under award numbers HL93149 (Katya Ravid) and HL084213 (Noyan Gokce). Click on the following link to view the study online: http://dx.plos.org/10.1371/journal.pone.0040584.

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