Diabetes research discovers protein that controls release of insulin
6 December 2016
A team led by Deputy Director Professor Peter Shepherd and Affiliate Investigator Dr Brie Sorrenson has uncovered a new mechanism that controls the release of insulin in the body.
The research was supported by a $1.2 million project grant from the Health Research Council of New Zealand (HRC) and was published in The Journal of Biological Chemistry.
Insulin regulates blood sugar levels and, in type 2 diabetes, a person either can’t make enough insulin, or the body’s cells are unable to identify the insulin that is already present.
The research discovery extends initial findings made by the group in 2013 and conclusively demonstrate that a protein known as beta-catenin is crucial for controlling the release of insulin from the pancreas to the blood by either blocking or allowing insulin to get through.
Professor Shepherd likened the mechanism to a volume control on a TV.
Between 50 and 60 per cent 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.
The research team focused on a genetic variant called TCF7L2. The genetic variant has been known to science for about 10 years and is the biggest contributing factor as to whether people are genetically susceptible to getting type 2 diabetes.
“We wanted to understand how the gene variants in TCF7L2 affect the regulation of glucose metabolism in the body,” Dr Sorrenson said.
“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.”
The findings potentially open up a whole new drug discovery field to understand how beta-catenin levels could be manipulated to control the release of insulin.
“The discovery could lead to more targeted medications, instead of a ‘one size fits all’ approach that currently exists for type 2 diabetes management,” Professor Shepherd said.
Sorrenson, B et al. (2016). A Critical Role for β-Catenin in Modulating Levels of Insulin Secretion from β-Cells by Regulating Actin Cytoskeleton and Insulin Vesicle Localization. The Journal of Biological Chemistry, Vol 291.
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