Insulin is secreted from the beta cells located in the pancreas, and the hormone is crucial for the maintenance of normal blood sugar levels. Deficiency of insulin leads to diabetes, characterized by elevated blood sugar. Diabetes most commonly presents in childhood as type 1 diabetes and in adults as type 2 diabetes.
Sometimes diabetes is diagnosed in very small babies, during the first six months of life. In these cases, mutations in the gene encoding insulin are often found.
These mutations are only found in one copy of the gene; that means that half of the produced insulin is normal, which should be enough to secure normal blood sugar. However, this is not the case: Insulin secretion stops totally after a few months. It is believed that this is caused by a toxic effect of the mutant insulin inside the cell, but 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.
“We now had the chance to test this with real patient-derived cells,” says Professor Timo Otonkoski from the University of Helsinki.
The researchers created a human disease model using stem cells from people carrying insulin gene mutations; then they 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 chronic stress, but their growth and development is disturbed. These effects are mediated through processes that could potentially be targeted by drugs,” Dr. Diego Balboa says.
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