DETROIT — A Wayne State University researcher is seeking to better understand what triggers the death of a type of cell that contributes to the onset of type 1 diabetes.

Beta cells in the pancreas make and release insulin, a hormone that controls blood glucose levels following a meal. Early in life, sometimes beginning at birth, the autoimmune system begins initiating destruction of islet beta cells, leading to the onset of type 1 diabetes. The precise mechanics of how that happens, however, still are unclear.

Anjan Kowluru, professor of pharmaceutical sciences, associate dean for external scientific affairs in the Eugene Applebaum College of Pharmacy and professor of internal medicine in the WSU School of Medicine, will use an animal model to test the effect of NSC23766, a compound more commonly called Rac inhibitor, to see if it will prevent or delay the onset of diabetes.

According to the American Diabetes Association, 25.8 million Americans — about 8.3 percent — have the disease, with about 7 million of those undiagnosed; another 79 million are prediabetic.

Kowluru’s study, “Tiam 1-Rac1 Signaling Axis Mediates Beta-Cell Dysfunction in Type 1 Diabetes,” is supported by a one-year, $110,000 grant from the Juvenile Diabetes Research Foundation.

“It appears that the Rac1 G protein is activated to initiate a series of signaling steps in beta cells to cause oxidative stress,” he said, “so if we can prevent activation of that protein with this inhibitor, in essence we are preventing the generation of oxidative stress and damage to the beta cell.”

Rac inhibitor already has been shown to have such an effect in the test tube; Kowluru hypothesizes a similar result in an animal model.

“We are excited to take this to the next step,” he said. “Success using an animal model would be a major breakthrough. We’re trying to better understand this process so that we are better able to prevent it.”

Although Kowluru’s study targets type 1 diabetes, it also may have implications for type 2 patients, whose disease onset comes later in life but often can be controlled through exercise and diet. While many tissues seem to be involved in generating oxidative stress, Kowluru said his team may be able to show that type 1 and 2 diabetes have a common signaling pathway involving Rac1 and oxidative stress.

“If we get a reasonably good clue from this study, then we will undertake long-term studies with different drug analogs,” he said. “We will synthesize compounds with better efficacy — biologically active with greater specificity — to see if they are tolerated, and then we could go into clinical trials. This study is the first step in that direction.”

Kowluru’s work in the area of diabetes also is supported by grants from the National Institutes of Health and the U.S. Department of Veterans Affairs, which has named him a senior research career scientist.


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