An antioxidant, heparan sulphate, may have a key role in the pathogenesis of type 1 diabetes by preventing loss of beta cells, Australian researchers have shown.

By protecting against oxidative damage the polysaccharide  appears essential for beta cell survival when insulin-producing cells are subject to autoimmune inflammation, according to new findings by researchers at the John Curtin School of Medical Research at the Australian National University, Canberra.

Building on their previous work in animal models, the researchers have shown that intervention in the early stages of type 1 diabetes to enhance levels of heparan sulphate may prevent progression of the disease.

Their in vivo research with beta cells from patients with type 1 diabetes provided evidence that intracellular heparan sulphate levels were depleted by heparanase enzymes from infiltrating leukocytes.

In further studies they showed that human beta cells were protected against autoimmune destruction when levels of intracellular heparan sulphate were enhanced.

The results provided further evidence that heparan sulphate played a critical role in the viability of beta cells, and also that levels of the glycosaminoglycan were a robust marker of type 1 diabetes progression, they concluded.

“Our findings raise the possibility that intervention therapy with dual activity heparan sulphate replacers or heparanase inhibitors could help to protect the residual beta cell mass in patients recently diagnosed with type 1 diabetes,” they suggested in PLOS One.

“Importantly, heparan sulphate replacers such as heparin … profoundly inhibit the catalytic activity of recombinant human heparanase, suggesting that as dual activity drugs, they could represent a new class of therapeutic for restoring beta cell heparan sulphate and blunting or preventing the progression of type 1 diabetes,” they added.

The researchers noted that until recently the focus of diabetes prevention research had been on blocking of T lymphocyte activation and cytokine responses with immunotherapies, but this had produced disappointing results.

New approaches were needed to preserve beta cell function, and their research suggested that it was worth exploring  the role of  polyscaccharides in preventing oxidative damage in beta cells.

“From a mechanistic standpoint, we propose that intracellular heparan sulphate normally preserves beta cell viability in situ by acting as a constitutive non-enzymatic antioxidant, providing immediate protection from damaging reactive chemical species,” they said.

“Heparan sulphate preservation therapy could [therefore represent a novel aid for beta cell rescue.”