Early research shows promise for therapeutics that delay type 2 diabetes


Vanderbilt researchers have discovered a unique pathway that initiates islet β cell inflammation—a hallmark of type 2 diabetes—putting them a step closer to developing targeted therapeutics for the disease that affects one in 10 Americans.

The article, “RIPK3-mediated inflammation is a conserved β-cell response to ER stress” was published in the journal Science Advances on Dec. 18.

Type 2 diabetes is caused when islet β cells in the pancreas fail to produce a sufficient amount of insulin—the hormone that maintains normal blood sugar levels in the body. Before they fail completely, islet cells become stressed and inflamed. The phenomenon of islet inflammation is well known, and the disease’s pathogenesis has been of interest to Wenbiao Chen, associate professor of molecular physiology and biophysics, throughout his career.

Chen’s lab found a protein—receptor-interacting protein kinase 3—that mediates islet inflammation and the consequent failure and death of β cells. To better understand the pathogenesis of type 2 diabetes, the researchers developed a zebrafish that is predisposed to developing the disease. In the zebrafish model, the researchers found that overeating causes an initial increase in islet β cells, but by the fourth day one-third of the β cells die, and the fish becomes diabetic.

“After screening a variety of chemicals for β cell protective drugs, we focused on a drug that inhibits RIPK3. While this protein is best known for cell death, we were surprised to learn that its function in islet β cells is to cause inflammation,” Chen said. They found RIPK3 is activated in the β cells by overeating and also found evidence that a similar response occurs in human β cells.

“It is well recognized that islet inflammation is a critical factor in the pathogenesis of type 2 diabetes, and now we have figured out one of the mechanisms that provoke this inflammation,” Chen said.

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