A new way to generate insulin-producing cells
Researchers from Karolinska Institutet in Sweden show how a molecule they have identified stimulates the formation of new insulin-producing cells in zebrafish and mammalian tissues, through a newly described mechanism for regulating protein synthesis. The results are published in Nature Chemical Biology.
“Our results point to a potential new target for the treatment of diabetes, in that we demonstrate a possible way to stimulate the formation of new insulin-producing cells,” says the study’s final author, lead researcher Olov Andersson. at the Department of Cellular and Molecular Biology of Karolinska Institutet.
Type 1 and type 2 diabetes are characterized by high blood sugar levels, the result of low levels of endogenous insulin, the hormone necessary for the absorption of glucose from the blood, or a physiological inability to use secreted insulin – or both.
Insulin injections and hypoglycemic drugs can control the disease, but not cure it.
Regeneration of pancreatic β cells
“An alternative could be a treatment that regulates blood sugar by increasing the number of pancreatic insulin-producing β cells, so we are studying the possible regeneration of these cells,” explains the first author of the study, Christos Karampelias, a former doctoral student at the Department. of Cellular and Molecular Biology at the Karolinska Institutet.
The Karolinska Institutet team previously identified a small molecule capable of stimulating the regeneration of insulin-producing β cells. They did this by analyzing a large amount of substances in a zebrafish model.
In this current study, they examined the molecular mechanism of this stimulation.
By analyzing a large number of molecular interactions in yeast cells, the researchers show that their molecule binds to a protein called MNK2. Subsequent studies in zebrafish and cell cultures indicate that the molecule works by regulating mRNA translation and stimulating protein synthesis, without which the formation of new β cells cannot be increased. Zebrafish given the molecule also showed lower blood glucose levels than controls.
The study also shows that the molecule can induce the formation of new pancreatic β cells in pigs and stimulate the expression of insulin in human organoids (organ-like cell formations).
Human tissue studies
“We will now study the effect of this molecule and similar molecules in human tissues and analyze the molecule’s target protein, MNK2, in the tissues of healthy donors and donors with diabetes,” explains Dr Andersson.
The molecule studied was found through studies in zebrafish, providing a valuable model for testing a large number of potential diabetes drug candidates. Since the fish embryo is transparent, its development is easy to follow under a microscope. Zebrafish larvae also have only one cluster of β cells, a so-called islet of Langerhans, which facilitates studies on the formation of new β cells after population decline in a way that mimics the onset of type 1 diabetes.
The study was funded by the European Research Council, the Swedish Research Council, the Ragnar Söderberg Foundation, the Novo Nordisk Foundation, the Strategic Research Program in Diabetes (SRP Diabetes) and the Strategic Research Area in stem cell research and regenerative medicine (StratRegen) at the Karolinska Institutet.
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