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A gut-derived protein could yield diabetes therapy

A gut-derived protein could yield diabetes therapy

Researchers have identified a protein produced by gut microbes that raises hope for developing therapies to treat Type 1 diabetes in adults.
Illustration of a person looking into the gut with a magnifying glass
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Researchers at the University of Oregon have identified a protein produced by gut microbes which induces the development of insulin-producing pancreatic cells. The outcome raises hope for developing therapies to treat Type 1 diabetes in adults.

The protein, Beta Cell Expansion Factor A or ‘BefA’, is understood to play a role in the proliferation of pancreatic beta cells in the developmental stages of animals and humans. Pancreatic beta cells are responsible for producing insulin in the body.

The researchers are now trying to fathom whether boosting the levels of this protein in older adults can stimulate the growth of beta cells. Such a development can help to treat Type 1 diabetes in which the body’s immune cells attack and kill its own insulin-producing cells.

“We don’t know yet whether these microbiota-derived proteins can stimulate proliferation of beta cells in older animals or in people, but that is a question we are currently pursuing,” Karen Guillemin, a professor at the Institute of Molecular Biology, University of Oregon, and author of the study told Happiest Health.

When cell membranes leak

Guillemin has spent over a decade researching the gut microbiome and the role it can play in tissue development. In that time, she has conducted experiments with zebra fish, mice and cultured cells to understand what the protein does. So far, the major function of BefA seems to be making cell membranes ‘leaky’.

Her hypothesis is that bacteria in the gut do this to target cell membranes of other microbes that live in the gut. The consequence of this is that BefA makes the membranes of other cells in our bodies leaky as well.

“There is some evidence that when beta cells experience membrane leakiness, it leads to elevated calcium levels in the cells, making them proliferate,” she adds.

Enhancing beta cell creation

To gather evidence of this the researchers conducted experiments in which they found that mice that lacked significant load of gut microbiota had fewer beta cells compared to mice with sufficient gut microbiota.

While this helped to prove that the BefA protein influenced pancreatic beta cell development, the researchers say they still need to do more work to understand the working mechanism of the protein. The hope is that this can lead to improved models for enhancing beta cell production in the human body.

The researchers are now conducting experiments on mice to gauge the efficacy of the protein as a drug  that can increase beta cell production. They have already shown that BefA can be administered orally or injected into the blood stream to have an effect.

Predicting and preventing Type 1 Diabetes

Guillemin says the work could yield a bunch of breakthroughs, the first being using the BefA protein as a drug to enhance beta cell development in adults suffering from Type 1 diabetes. The other could be a diagnostic test to predict if infants are at risk of developing the lifelong disorder.

“It may be possible to perform microbiome profiling combined with other genetic and environmental data to predict whether infants are at high risk for developing T1D,” says Guillemin. She adds  that a prophylactic administration of the protein-producing gut bacteria in the first two years of life of these babies could give them a life-long pool of beta cells.

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