Protein centred on for diabetes drug development

By Wai Lang Chu

- Last updated on GMT

Related tags: Insulin

Scientists have isolated a single protein that has a key role in
diabetes development, which could form the basis for new drug
therapies that could effectively treat a disease that has become
endemic.

At the last count in 2006, the World Health Organisation (WHO) estimates at least 171m people worldwide suffer from diabetes. Its incidence is increasing rapidly, and it is estimated that by the year 2030, this number will double.

The discovery centres on the protein calcineurin, which has been shown to regulate a total of ten genes that have been linked to the condition. A defect in the supply of the protein decreases production of the pancreatic beta cells that produce insulin.

Experimenting on mice, the Stanford University team bred the animals to produce calcineurin in the pancreas only until they were born. After birth, protein production stopped.

By stopping the production of calcineurin, the number of beta cells stayed constant rather than increasing as the mice grew. By 12 weeks of age, the mice were severely diabetic as the existing numbers of beta cells were unable to produce enough insulin.

"This work has led us and others to think in entirely new ways about diabetes,"​ said researcher Dr Jeremy Heit in the study.

"Until now people had identified individual genes or processes that were involved in diabetes. The new findings show that these lines of research are connected through a common regulator in calcineurin."

In diabetes, the beta cells do not produce enough insulin or none at all, which prevents the body from being able to take in sugar after a meal. Sugar accumulates in the blood, damaging the blood vessels, kidneys and eyes.

The study also focused on ways to produce normal amounts of insulin. One method focused on activating its protein partner, NFAT. Active NFAT behaved normally, multiplying as the mice aged and producing normal amounts of insulin.

The scientists thought that therapies that enhance calcineurin or NFAT activity could become a viable treatment for type-2 diabetes, in which the beta cells do not produce enough insulin.

Additionally, activating calcineurin could enable scientists to direct embryonic stem cells to become insulin-producing cells.

Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence is, however, expected to occur in Asia and Africa, where most patients will likely be found by 2030.

The increase in incidence of diabetes in developing countries follows the trend of urbanisation and lifestyle changes and a "Western-style" diet.

This has suggested an environmental (i.e., dietary) effect, but there is little understanding of the mechanism(s) at present, though there is much speculation.

Related topics: Preclinical Research

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