Diabetes Missing Link Discovered

New Zealand researchers have discovered a new mechanism which controls the release of the hormone insulin in the body, giving hope for those with a genetic susceptibility to type 2 diabetes.

The findings, published today in the Journal of Biological Chemistry, show for the very first time that a protein known as beta catenin is critical for controlling the release of insulin from the pancreas to keep steady  blood sugar levels.

In type 2 diabetes, either the body doesn’t produce enough insulin or the insulin that’s present, resulting in high levels of sugar isn’t recognised by the cells in the body.

University of Auckland lead researcher Prof. Peter Shepherd and his group, such as Brie Sorrenson, Ph.D., completed the study with the aid of a $1.2 million project grant from the Health Research Council of New Zealand (HRC).

For this part of the project they concentrated on a variant in a gene. This variant was known to science for approximately 10 years and is the largest contributing element for whether individuals are genetically susceptible to getting type 2 diabetes or not.

“We wanted to know what happens in the body’s cells which are associated with TCF7L2 and how the processes that go on affect the regulation of glucose metabolism within the body,” said Shepherd.

“TCF7L2 binds directly to beta catenin. By detecting this interaction, we discovered that beta catenin levels not only alter in reaction to rising and falling nutrient levels, but that they also modulate how much insulin we have within our body and make sure that we have the perfect amount of insulin at the right time.”

“Researchers have built up a large body of knowledge over the past 15 years about how hormones are released from cells within the body, but that is the first time that this mechanism was associated with the release of insulin,” said Shepherd.

“One potential reason for this delay is that beta catenin has in the past been closely associated with cancer, not even diabetes.

“Under the cell membrane you will find layers of fibers called actin. These fibres form networks which somehow bind to insulin,” he added.

“Our evidence suggests that beta catenin is commanding these networks of actin fibers and rapidly changing their nature by opening up ‘openings’ in the fiber system to either block or allow the discharge of insulin.”

Though this paper focuses specifically on type two diabetes, the team’s preliminary findings as part of this broader HRC-funded project suggest that the same mechanism also can help control the manner insulin functions; the metabolism of glucose in fat cells; and the release of hormones within the brain that control appetite and energy metabolism.

“We think we have identified a much broader mechanism which affects multiple cell types, not just beta cells within our own pancreas,” said Shepherd.

HRC Chief Executive Professor Kath McPherson states unless we understand the chemistry behind them we can’t create new therapies for chronic diseases like diabetes and this is one of the reasons.

“Peter and his team have obtained considerable HRC funding through the years to pursue this avenue of research,” she said.

“Major impacts like this highlight the benefits of long-term HRC funding for emerging science from New Zealand. It is hard work finding new mechanisms that contribute to disease.

“There is a really high payoff in the end concerning improving our understanding of disease and developing possible new therapies,” said McPherson.

Between 50 and 60 per cent of individuals who are vulnerable to type 2 diabetes within our surroundings have a genetic variant that puts them at risk of getting the disease.

“This discovery potentially opens up a completely different drug discovery discipline to comprehend how we could control  beta catenin  levels to control the discharge of insulin,” reasoned  Shepherd.

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