Yale University researcher Andrew Miranker and his team have proposed a potential treatment for diabetes, which focuses on a hormone found in all humans. The research was published in the April issue of Nature Communications.

The progression of diabetes is tied directly to the health of insulin-producing pancreatic islet β-cells, which coordinate the release of insulin in response to changes in blood glucose. There are drugs that treat diabetes by stimulating alternative ways for the body to use or eliminate glucose, but there are no approved drugs available to address the causes of type 2 diabetes.

Miranker’s lab is focused on a protein partner to insulin, known as islet amyloid polypeptide (IAPP). It is a hormone co-secreted with insulin from the pancreatic islet β-cells. In its healthy state, IAPP works alone but the toxic version of IAPP is formed from tens to hundreds of copies of the protein. Miranker’s results support a model whereby IAPP-mediated toxicity derives from large, mitochondrial membrane-associated assemblies of IAPP.

The research team has discovered that when IAPP adopts the wrong shape, it pokes holes in the membranes of islets large enough to kill the insulin-secreting cells. “If we ameliorate these very large holes by designing a compound to target a particular IAPP structure, we can prevent toxicity,” says Miranker.

Miranker lab has thus developed a drug lead, ADM-116, that binds to IAPP and can rescue insulin-secreting β-cells. Researchers are planning to translate these discoveries into drugs to improve the long-term health of these cells. Although the researchers are currently focusing on type 2 diabetes, the approaches they have developed may also apply to Alzheimer’s and Parkinson’s diseases.

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