Researchers from the John Curtin School of Medical Research in Canberra, Australia have discovered that the insulin-producing beta cells need a complex sugar, heparan sulfate, for their survival and without it they die. Replacement of heparan sulfate in the beta cells rescues the cells from dying in culture and protects them from oxidative damage.
Prof. Christopher R. Parish, Dr. Charmaine J. Simeonovic, and their team used the NOD mouse model of spontaneous type 1 diabetes which closely resembles the disease in humans, to identify this previously unrecognized mechanism of beta cell destruction. During the development of type 1 diabetes in the NOD mouse, the researchers found heparan sulfate was progressively lost from the pancreatic islets and islet beta cells.
This new work has identified heparan sulfate depletion from beta cells as a novel mechanism for inducing beta cell death, which the researchers attribute to the removal of the beta cells’ normal defense against oxidative damage by free radicals. The study further demonstrated that the autoimmune cells of the immune system which are responsible for beta cell damage do so by producing the enzyme heparanase which degrades heparan sulfate in the islet beta cells. Treatment of the mice with a heparanase inhibitor PI-88 was shown to preserve the islet heparan sulfate and protect NOD mice from type 1 diabetes.
This study has revealed a new understanding of the development of type 1 diabetes and has identified a new therapeutic strategy for preventing type 1 diabetes progression and associated complications.
The study was published in the Journal of Clinical Investigation.