Molecular makeover targets insulin longevity

From Monash Magazine, February 2013:

“Nature may have come up with a beautiful design in the insulin molecule, but that doesn’t mean it can’t be improved,” says Associate Professor Andrea Robinson from Monash University’s School of Chemistry.

Regular doses of insulin are essential to the health of almost 300 million people around the world who have diabetes. Their bodies produce little or no insulin, which is needed to turn glucose from food into energy.

But insulin in its natural form, or in the available synthetic forms, must be kept at four degrees Celsius or it loses its potency. “If you can’t keep milk, you can’t keep insulin,” Associate Professor Robinson says. That creates a logistical problem when it comes to distributing insulin to areas such as remote Australia and much of the developing world.

At higher temperatures, the insulin molecule’s shape changes and it can no longer interact with receptors on cells to regulate glucose metabolism.

A key to understanding this instability can be found in insulin’s disulfide framework. If any one of these sulfur bridges breaks, the insulin molecule unravels into a form that not only exposes it to the risk of breaking down, but also means it can no longer interact with its receptor in the body and activate the required insulin response. The same goes for synthetic insulin, the life-saving replacement for people whose bodies do not produce any or enough insulin.

These sulfur atom bridges provide Associate Professor Robinson with an ideal target in her quest to strengthen the insulin molecule. Developments in the work on this unstable molecule mean that there could soon be a form of synthetic insulin that can resist higher temperatures, a factor that could simplify the storage of therapeutic insulin. Read more.

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