Heparin Sulfate and Heparanase Play Key Roles in Mouse Beta Cell Survival and T1D

The area surrounding cells in the body is a complex mixture of proteins, sugars and other molecules that can provide structural support for tissues and cells, provide mechanical protection and serve as a reservoir of growth factors. In this report, Dr. Simeonovic’s team demonstrated that heparin sulfate, a major component of the space surrounding islets, is critical for beta cell survival. In mouse models of T1D they showed that immune cells act to break down the heparin sulfate in the surrounding space, contributing to the demise of the beta cells. The team showed that islets are normally surrounded by a robust matrix of heparin sulfate and that during their islet isolation and culture this matrix is lost, correlating with the reduction in beta cell survival over time in culture. Replacement of heparin sulfate restored the health and survival of lab grown beta cells. The group also found that immune cells infiltrating the islets in mouse models of T1D produce high levels of an enzyme capable of breaking down heparin sulfate and that inhibition of this enzyme activity protected mice from autoimmune diabetes. This work suggests that therapeutic strategies to maintain levels of heparin sulfate in the space around the islets in T1D could be effective at protecting beta cells and slowing their destruction by the immune system.

Reference:

Ziolkowski AF, Popp SK, Freeman C, Parish CR, Simeonovic CJ. Heparan sulfate and heparanase play key roles in mouse beta cell survival and autoimmune diabetes. J. Clin. Invest. 2012;122:132-140.

Ramifications for Individuals with Type 1 Diabetes:

This work in mice describes a novel role for a component of the mixture of material surrounding beta cells in promoting beta cell survival and conferring beta cell protection in mouse models of T1D. Further work will be required to determine if the same pathway is relevant for human beta cells and to identify drug targets and develop therapeutics to maintain the normal environment surrounding islets in people with T1D.

JDRF Involvement:

None.