T1D is a disease involving beta cell destruction and death that is largely undetectable until the point at which a person needs to begin insulin injections. There is a need to identify unique markers of beta cell injury and develop blood-based assays to directly measure the extent of beta cell injury in diabetic animal models and in humans. Here Dr. Martens’ group proposes using a protein called PPP1R1A as a novel marker for acute beta cell destruction. This protein was identified from purified beta cells and is specific to beta cells. In cultured cells, PPP1R1A was released from chemically-injured rat and human islets in proportion to the extent of beta cell death. In a rat diabetic model, this protein was progressively depleted in disintegrating beta cells and discharged into the blood. Finally, in a pilot study, a similar massive PPP1R1A discharge in blood was also detected in 3 patients immediately after islet transplantation which correlates with the known high degree of beta cell death immediately post-transplantation. These findings provide the first demonstration of PPP1R1A as a potential real-time marker of beta cell destruction in animal models and patients, and warrants development of more sensitive methods for its further validation in clinical trials.
Ramifications for Individuals with T1D:
These findings provide the first evidence for PPP1R1A as a potential real-time marker of beta cell destruction in animal models and patients, and warrants development of more sensitive methods for its further validation in clinical trials. Such a marker of beta cell death could help assess the disease progress in individuals at risk of T1D early in the disease process before a clinical diagnosis and after diagnosis and could help speed clinical trials of new beta cell regeneration therapies by providing a sensitive measure of beta cell health.
Investigators and Institutions:
Jiang L, Brackeva B, Ling Z, Kramer G, Aerts JM, Schuit F, Keymeulen B, Pipeleers D, Gorus F, Martens GA.
Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium.
Jiang L, Brackeva B, and others. Potential of protein phosphatase inhibitor 1 as biomarker of pancreatic beta cell injury in vitro and in vivo. Diabetes. 2013 Aug;62(8):2683-8. doi: 10.2337/db12-1507. Epub 2013 Apr 4.