The first centennial of the discovery of insulin was marked in 2021, when Frederick Banting and Charles Best isolated insulin from animal pancreas to cure a diabetic dog, lowering its blood sugar levels in two hours.

It was the start of a new era in the treatment of diabetes, a condition that had been known for millennia but lacked a really effective therapy until then. Insulin’s discovery represented a turning point in the lives of people with diabetes all around the world, and without it, their current day-to-day lives would be very different.

However, scientists want to go even further and are even discussing the possibility of curing diabetes. How?

Insulin is a necessary hormone generated by beta cells in the pancreas. The breakdown of these cells causes type 1 diabetes, which requires patients to restore missing insulin with repeated daily injections.

Beta cells obtained from a brain dead organ donor’s pancreas can be transplanted into diabetic patients to restore insulin secretion. However, because cells from at least two donors are required to cure one diabetic, this treatment has not been generally adopted.

Attempts have been done for a long time to grow functioning beta cells from stem cells, which could make this treatment more widespread. However, beta cells derived from stem cells have so far been immature, with insulin production that is poorly controlled. This could explain why no advancements have been made in therapeutic studies based on immature cells now being conducted in the United States.

“Pancreatic islet transplants derived from stem cells are no longer science fiction,” Diego Balboa admits. “Since 2014 there have been clinical trials in the US in which people with type 1 diabetes have been transplanted with these cells and there are currently several open clinical trials that are showing promising preliminary results.”

Professor Timo Otonkoski’s research group at the University of Helsinki has pioneered efforts to improve the functionality of pancreatic cells derived from stem cells.

The research has proved, for the first time, that stem cells may create cells that nearly resemble normal pancreatic islets in terms of structure and function, in a recently published article.

The work was published in the journal Nature Biotechnology, and it was largely supported by the Academy of Finland’s MetaStem Center of Excellence.

“In our study, insulin secretion was regulated as usual in cells, and the cells responded to changes in the glucose level even better than the pancreatic islets isolated from organ donors that were used as controls,” explains Väinö Lithovius.

The most in-depth examination of beta cell activity to date

In both cell cultures and mouse trials, the researchers demonstrated the function of stem cell–derived beta cells. The researchers showed that stem cell–derived beta cells transplanted into mice efficiently managed the mice’s glucose metabolism in the latter study.

“Blood glucose levels are higher in mice than in humans, roughly 8–10 millimolar. After the cell transplantation, the level decreased to that seen in humans, roughly 4–5 millimolar. It remained at this level, proving that the stem cell–derived transplant was capable of regulating blood glucose levels in mice,” adds researcher Jonna Saarimäki-Vire.

The new study of beta cell function is the most complete yet: in addition to insulin production, the researchers looked into the functionality of systems that regulate insulin secretion, such as metabolism and ion channels, and linked their findings to gene expression during development.

“Our study will help further improve the production of stem cell islets, which will make it easier to utilise them in disease modelling and cell therapies,” Timo Otonkoski adds.

Source: 10.1101/2021.03.31.437748

Image Credit: Getty

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