Scientists Work to Discover Mechanisms Behind Neonatal Diabetes

Sometimes diabetes is diagnosed very early on in small babies, and researchers at the University of Helsinki are doing more to understand why, in hopes of one-day developing drugs for the prevention of this, and more common forms of diabetes.

To understand the mechanisms better, the team in Finland was able to look at the mutations in the gene encoding insulin in real patient-derived cells.

“These mutations are only found in one copy of the gene,” Dr. Timo Otonkoski states in a press release, “that means that half of the produced insulin is normal, which should be enough to secure normal blood sugar.”

However, Otonkoski indicates this is not the case: and insulin secretion stops totally after a few months.

The Finnish researchers believe this is caused by a toxic effect of the mutant insulin inside the cell, but the researchers say the exact mechanisms are poorly understood.

Mutant insulin is known to cause a chronic stress reaction in the beta cell, and it has been thought that this leads to the death of the cell.

“It is important to understand the detailed consequences of beta-cell stress, because this may help to develop drugs for the prevention of both rare and common forms of diabetes,” Otonkoski comments, “we now had the chance to test this with real patient-derived cells,” he says.

How was the Study Conducted?

Researchers created a human disease model using stem cells from people carrying insulin gene mutations.

They then corrected cells using a gene-editing technique called CRISPR.

The mutant and corrected stem cells were then induced to turn into insulin-secreting beta cells and the researchers followed the function of the cells after transplanting them in mice.

“The main finding of the study was that these cells do not die from the chronic stress, but their growth and development is disturbed,” explains Dr. Diego Balboa, “these effects are mediated through processes that could potentially be targeted by drugs” he adds.

In this study, the authors describe mechanisms linking chronic cellular stress to the poor development of the insulin-producing cells.

“A strongly reduced number of beta-cells will cause diabetes immediately,” they state, “but even a milder defect will increase the risk of diabetes later in life,” they say, “understanding the molecular mechanisms of these processes may help in devising ways to preserve the mass and function of beta cells,” Otonkoski states.

The research has been published in the journal, eLife.