Reprogramming islet alpha cells to produce insulin, bringing hope to diabetes treatment

Reprogramming islet alpha cells to produce insulin, bringing hope to diabetes treatment

April 03, 2019 Source: Nature Natural Science Research

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Insulin-free islet cells can be reprogrammed to produce insulin and help control blood glucose levels in diabetic mice.

There is a type of insulin-producing cells in the pancreas that can cause diabetes if damaged. But a recent study shows that other cells, after reprogramming, can replace this insulin-producing cell and help control blood sugar levels.

The results of this study have given patients hope: "reprogramming" insulin-producing cells or can be used to treat diabetes. However, this method is currently only tested on mice using human cells.

In a study published in Nature on February 13, the researchers reported how to induce normal islet-free human islet cells to change their identity and begin to produce insulin, a hormone that regulates blood sugar levels [1].

When these reprogrammed cells are implanted into mice, the symptoms of diabetes in the mice are alleviated, greatly increasing the likelihood that the method will be used to treat diabetes in humans.

“I think this method has great potential,” said Terence Herbert, a biologist at Lincoln University in the UK. However, he also said that the research is still in its infancy and that several obstacles need to be overcome to truly achieve clinical application.

system breakdown

After eating, blood sugar levels will rise. Under normal circumstances, beta cells in the pancreas release insulin accordingly, and insulin stimulates cells to absorb sugar. However, in diabetic patients, this system does not work properly, leading to high blood sugar, which damages the body and causes disease.

In type 1 diabetes, the immune system attacks and destroys islet beta cells; in type 2 diabetes, islet beta cells are unable to produce sufficient insulin, or the body is resistant to insulin.

Scientists have previously shown through mouse studies that if islet beta cells are destroyed, another type of islet cell alpha cells will become insulin-like like beta cells. Alpha cells generally produce glucagon, which coexists with beta cells in a cell mass that secretes hormones, that is, islets. Past mouse studies have shown that two proteins that control gene expression appear to play an important role in inducing alpha-cell production of insulin: Pdx1 and MafA.

Human factor

Pedro Herrera of the University of Geneva in Switzerland and colleagues wondered if there would be similar effects if more Pdx1 and MafA were produced in human alpha cells.

First, they extracted islet cells from human pancreas and isolated different types of islet cells. They then introduced DNA encoding the Pdx1 and MafA proteins into alpha cells and re-aggregated them together.

After a week of culture, nearly 40% of human alpha cells produce insulin, while control cells that have not been reprogrammed do not. In reprogrammed cells, the expression of other genes associated with beta cells is increased. "They have mixed features," Herrera said.

Subsequently, the Herrera team implanted reprogrammed cells into diabetic mice whose beta cells had been damaged and found that the blood glucose levels in the mice had dropped to normal levels. After the reprogrammed cells were removed, the blood glucose levels of the mice rose again.

Change identity

Herrera said that if alpha cells or other types of islet cells are treated in this way to produce insulin in diabetic patients, the quality of life of patients is expected to be greatly improved. Herrera said their dream was to find a drug that would turn alpha cells into identity.

But he also admits that there is still a long way to go to realize this dream. First, his team needs to figure out what changes have occurred at the molecular level when alpha cells become beta-cells.

Other teams are also trying to create new insulin-producing cells in the pancreas: some try to use stem cells to produce beta cells. But in type 1 diabetes, the immune system attacks beta cells, which is a big challenge for such strategies.

Herbert said Herrera and his team used some evidence to prove that their hybrid cells are not susceptible to this attack and that their method is more feasible than the stem cell approach.

But Herbert added that before the authors come to a strong conclusion that the method is effective, they need to do further testing: test the effect of this method in the presence of other antibodies that attack beta cells in patients with type 1 diabetes. .

Islet cell plasticity

Inducing insulin production in certain islet cells without actually becoming beta cells is a fascination with Inês Cebola, an islet biologist at Imperial College. "That is very shocking."

The islet biologist Diego Balboa Alonso of the Barcelona Genome Control Center also shares the same view. He said that the latest research results show that the plasticity of the human pancreatic hormone system is much higher than previously expected. “This excellent study proves this.”

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