Heparan sulfate is a molecule that is found on the surface of most cells and controls the interactions between various proteins. In this study, the investigators explored the idea that preservation of heparan sulfate in islets could be a therapeutic strategy for preventing T1D. They found that cells involved in the destruction of beta cells produce heparanase, an enzyme that leads to the loss of heparan sulfate. When the investigators treated animals with an inhibitor of heparanase, mice were protected from developing T1D and heparan sulfate in islets was preserved. In support of these animal studies, the lab assay also showed that the inhibitor of heparanase prevented beta cell death. Furthermore, when the investigators examined the islets of the test mice at different stages of disease, they found that islets without inflammation still contained heparin sulfate, whereas islets with inflammation showed lower heparin sulfate levels. Islet inflammation often leads to the destruction of beta cells in diabetic mice.
Ziolkowski AF, Popp SK, Freeman C, Parish CR, Simeonovic CJ. (2012). Heparan sulfate and heparanase play key roles in mouse beta cell survival and autoimmune diabetes. J Clin Invest. Jan 3;122(1):132-41.
Ramifications for Individuals with Type 1 Diabetes:
These findings show a critical role of islet heparin sulfate in beta cell survival and highlight the potential for new therapeutic approaches for rescuing beta-cell function at the time of T1D onset by blocking progressive loss of islet-associated heparin sulfate during disease development with heparanase inhibitors.
This work was supported by a National Health and Medical Research Council of Australia/JDRF Special Program Grant in Type 1 Diabetes as well as a research grant from the Roche Organ Transplantation Research Foundation/JDRF.