NZ study could offer new hope for type-2 diabetes

Type-2 diabetes usually develops in adults but it is becoming more common in children, and is the...
Type-2 diabetes usually develops in adults but it is becoming more common in children, and is the only type linked with obesity. Photo: Christine O'Connor

A million-dollar Kiwi study has revealed a new mechanism in the body that could offer new hope for those with a genetic susceptibility to type 2 diabetes.

Findings published today show for the first time that a protein known as beta-catenin is crucial for controlling the release of insulin from the pancreas to maintain stable blood sugar levels.

Most of the 240,000 sufferers of diabetes in New Zealand have type-2 diabetes, in which either the body doesn't produce enough insulin or the cells in the body don't recognise the insulin that is present, leading to high levels of glucose in the blood.

Type-2 diabetes usually develops in adults but it is becoming more common in children, and is the only type linked with obesity.

Between 50 and 60% of people who are susceptible to type 2 diabetes in our current environment also have a genetic variant that puts them at higher risk of getting the disease.

In a new study, an Auckland University team led by Professor Peter Shepherd focused on a recently-identified variant in a gene called TCF7L2.

Over the past decade, the variant has become known as the biggest contributing factor as to whether people are genetically susceptible to getting type 2 diabetes or not.

"We wanted to understand how the gene variants in TCF7L2 affect the regulation of glucose metabolism in the body," Prof Shepherd said.

They observed how TCF7L2 binded directly to the beta-catenin protein, whose levels not only changed in response to rising and falling nutrient levels, but also regulated how much insulin was ready for secretion and ensured the body had the right amount of insulin at the right time.

"It's like the volume control mechanism on your phone or TV."

The discovery potentially opened up an entire new drug discovery field to understand how beta-catenin levels could be manipulated to control the release of insulin.

While scientists have built up a large body of knowledge over the past 15 years about how hormones are released from cells in the body, this was the first time beta-catenin has been associated with insulin release mechanisms.

One possible reason for this delay was that beta-catenin had in the past been closely associated with cancer, not diabetes.

"Underneath the cell membrane there are layers of fibres called actin," Prof Shepherd explained.

"These fibres form networks that somehow bind to the small granules containing insulin."

His team's research suggested that beta-catenin was controlling these networks of actin fibres and rapidly changing their nature by opening up "gaps" in the fibre network to either block or allow the release of insulin.

The $1.2 million study was part of a wider, Health Research Council-funded project whose preliminary findings suggested the same mechanism also helped control the way insulin functions, the metabolism of glucose in fat cells and the release of hormones in the brain that controlled appetite and energy metabolism.

"We think we've identified a much broader mechanism that affects multiple cell types, not just beta cells in our pancreas."

Health Research Council chief executive Professor Kath McPherson said new treatments for chronic disease like diabetes couldn't be developed unless scientists could first understand the biology behind them - something that made fundamental research so important.

"It's hard work finding new mechanisms that contribute to disease - researchers must go down a lot of blind alleys to find them," she said.

"However, there's a very high payoff in the end in terms of enhancing our understanding of disease and developing potential new treatments."

The findings have been published in The Journal of Biological Chemistry.

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