High-resolution model of six insulin molecules assembled in a hexamer. Credit: Isaac Yonemoto/Wikipedia
NZ researchers have uncovered a new mechanism that controls the release of insulin in the body, providing hope for those with a genetic susceptibility to type 2 diabetes. The findings show for the first time that a protein, beta catenin is crucial for controlling the release of insulin from the pancreas to maintain stable blood sugar levels. They focused on a variant in a gene called TCF7L2. This variant has been known to science for about 10 years and is the biggest contributing factor for whether people are genetically susceptible to getting type 2 diabetes or not.
“We wanted to understand what happens in the body’s cells that are associated with TCF7L2 and how the processes that go on affect the regulation of glucose metabolism in the body,” says Professor Shepherd. “TCF7L2 binds directly to beta catenin. By observing this interaction, we found that beta catenin levels not only change in response to rising and falling nutrient levels, but that they also regulate how much insulin we have in our body and ensure that we have the right amount of insulin at the right time.”
“Underneath the cell membrane there are layers of fibres called actin. These fibres form networks that somehow bind to insulin,” he says. “Our evidence suggests that beta catenin is 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.”
Although this paper focuses specifically on type 2 diabetes, the team’s preliminary findings as part of the wider HRC-funded project suggest that the same mechanism also helps control the way insulin functions; the metabolism of glucose in fat cells; and the release of hormones in the brain that control 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,” says Professor Shepherd.
“Major outcomes like this highlight the benefits of long-term HRC funding for emerging science in New Zealand. It’s hard work finding new mechanisms that contribute to disease – researchers must go down a lot of blind alleys to find them. “There’s a very high payoff in the end in terms of enhancing our understanding of disease and developing potential new treatments,” says Professor McPherson.
Between 50 and 60% of people who are susceptible to type 2 diabetes in our current environment have a genetic variant that puts them at higher risk of getting the disease. “This discovery potentially opens up a whole new drug discovery field to understand how we could manipulate beta catenin levels to control the release of insulin,” says Professor Shepherd.
https://www.fmhs.auckland.ac.nz/en/faculty/about/news-and-events/news/2016/12/5/diabetes-missing-link-discovered-in-auckland.html http://phys.org/news/2016-12-diabetes-link.htmljCp
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