A gene linked to type 2 diabetes may offer clues to new therapies, British researchers say.
The scientists have been examining a variation in the gene SLC30A8.
This gene encodes a protein which carries zinc, which is needed by insulin to develop into the correct shape in pancreas cells. It is already known that certain variations in this gene can reduce the risk of type 2 diabetes, but the reason was unknown.
Professor Anna Gloyn of the Wellcome Centre for Human Genetics, University of Oxford, UK, and colleagues looked at a specific allele in SLC30A8, which tends to occur in Western Finland, and protects against type 2 diabetes.
They recruited relatives of identified carriers and measured their insulin response to a meal containing sugar.
This group showed “better insulin secretion due to enhanced glucose responsiveness and proinsulin conversion”, the researchers reported earlier this month in Nature Genetics.
In further lab tests, they showed that this particular allele “results in reduced SLC30A8 expression”, leading to increased glucose responsiveness.
Co-author Dr Tiinamaija Tuomi, from Helsinki University, Finland, added: "We compared people with the mutation with their relatives who do not have the mutation, but who have similar genetic background and lifestyle. This way, we could make sure that the effects we were seeing were definitely because of this gene, and not because of another genetic or life-style factor."
Professor Gloyn commented: "We found that this mutation had collateral consequences on key functions of pancreatic beta cells and during their development. Importantly, this study exposes the extraordinary molecular complexity behind a specific gene variation conferring risk or protection from type 2 diabetes.
"Our results position this zinc transporter as an appealing and safe target for antidiabetic therapies.”
Dwivedi, O. et al. Loss of ZnT8 function protects against diabetes by enhanced insulin secretion. Nature Genetics 1 November 2019; doi: 10.1038/s41588-019-0513-9
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