A new study by Vanderbilt researchers has identified a unique pathway that initiates islet β cell inflammation, thus bringing them closer to creating targeted therapeutics for Type 2 diabetes which affects at least one in ten Americans.
Researchers establish mechanism leading to type diabetes II
The researchers published the study, “RIPK3-mediated inflammation is a conserved β cell response to ER stress” in the Science Advances journal on December 18, 2020. Normally, Type II diabetes results when the pancreas’ islet β cells fail to produce adequate insulin to stabilize blood sugar levels in the body. Interestingly, before islets cells fail, they become inflamed and stressed. The islet inflammation phenomenon is well known and Wenbiao Chen who is molecular physiology and biophysics professional has been focusing on disease pathogenesis.
Chen’s lab identified a receptor-interacting protein kinase 3, which mediates islet β cell inflammation and subsequent β cell failure and death. Researchers came up with a zebrafish that is susceptible to developing diabetes in a bid to understand the disease’s pathogenesis. According to the zebrafish model, the researchers note that overeating results in initial islet β cells increase. Interestingly on the fourth day, almost a third of the β cells die and the fish develops diabetes.
RIPK3 function in islet β cells leads to inflammation
According to Chen, after screening various chemicals for β cell-protective drugs, the researchers focused on drugs inhibiting RIPK3. Although the protein leads to cell death, researchers were surprised to find that its function in β cells leads to inflammation. Chen added that they established that β cells activated RIPK3 by overeating and there was evidence of a similar process in human β cells. It is important to note that islet inflammation is a vital aspect ion type 2 diabetes pathogenesis but now researchers have established a mechanism that provokes this inflammation.
Most importantly, RIPK3 is present in most organs and tissues in the body and it sometimes produces an anti-inflammatory response in some tissues. Understanding how RIPK3 impacts β cells can help in coming up with targeted therapies for diabetes.