Self-assembling structures to treat diabetes

Scientists from the Birla Institute of Technology and Science, Pilani have developed a method by which lisofylline, a molecule with anti-diabetic properties, self-assembles into structures

that protect β cells of the pancreas from cell death1. It also improves insulin production, providing a novel method to treat type-1 diabetes. Type-1 diabetes is an auto-immune disease in

which the insulin-producing β cells of the pancreas are killed. Lisofylline suppresses pro-inflammatory cytokines, protecting β cells from death. It also preserves insulin secretion.

Although this molecule has significant clinical potential, its applications have been limited as it has a very short half-life and is rapidly metabolised to pentoxifylline (PTX). Thus, to

have any effect, it needs to be administered in very high doses – 25mg/kg twice daily. This conversion to PTX has been attributed to a secondary hydroxyl group in the side chain of

lisofylline. In a novel approach, the researchers protected this hydroxyl group by conjugating lisofylline to a fatty acid (linoleic acid). As lisofylline is hydrophilic and linoleic acid is

hydrophobic, this conjugated structure self-assembles into lipid spheres called micelles. The formation of micelles increased the half-life of lisofylline by 5.7 times, compared with free

lisofylline, and also reduced its clearance. Tested in type 1 diabetic mice, free lisofylline could reduce, but not maintain the low glucose levels. However, in mice injected with

lisofylline-conjugated structures, this reduction in glucose was stable and comparable to normal levels. Additionally, these mice showed reduced inflammatory cytokines, increased insulin

production and reduced death of islet β pancreatic cells. This method thus opens new avenues for treating type-1 diabetes or other auto-immune diseases.