In a promising discovery that could improve the clinical delivery of insulin for people with diabetes, scientists have developed a non-fibrillating form of human insulin.

Using a novel glycosylation technique, an international research team led by Associate Professor Akhter Hossain, PhD, from the Florey Institute of Neuroscience and Mental Health (the Florey), has successfully synthesized an insulin analogue called glycoinsulin that demonstrates the same glucose-lowering effects as native insulin in preclinical studies without fibril formation.

Fibrils can arise when insulin compounds aggregate together forming clumps. For people with diabetes who rely on pump infusions to administer insulin, fibrils pose serious risk in blocking the delivery of insulin, which can potentially lead to life-threatening underdosing.

“Not only did our research demonstrate that glycoinsulin does not form fibrils, even at high temperature and concentration, but also that it is more stable in human serum than native insulin,” Hossain said. “Together these findings could position glycoinsulin as an excellent candidate for use in insulin pumps and a way to improve the shelf life of insulin products…. We now hope to streamline the manufacturing process for glycoinsulin so this compound can be further investigated in larger clinical studies.”

Over 25,000 people in Australia and 350,000 people in the United States use insulin pumps as part of their diabetes management.

In what can cause significant patient burden and medicine wastage, insulin pump infusion sets are required to be replaced every 24 hours to 72 hours to mitigate the occurrence of fibrils. In the United States alone, more than $1 billion could be saved per year if the usage period for insulin increased from two to six days.

“Typically, the chemical modification of insulin causes structural destabilization and inactivation, but we were able to successfully synthesize glycoinsulin in a way that retains its insulin-like helical structure,” said Professor John Wade, PhD, who co-led the research. “The result is an almost fully active insulin analogue [that] has demonstrated near-native binding to insulin receptors in both lab and animal studies.”

Professor Greg Johnson, Diabetes Australia CEO, welcomed the research findings saying they had the potential to make life easier for those who use insulin pumps.

“It is nearly 100 years since the discovery of insulin and it’s very exciting that we see new discoveries for insulin, and insulin-like molecules, that have the potential to ease the day-to-day burden and cost for people with diabetes.”

This research was published in the Journal of the American Chemical Society.

This article was adapted from information provided by the Florey.

 

 

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