There are many small glands in the pancreas, the so-called islets of Langerhans. These glands release their messenger substances (hormones) into the bloodstream. The islets of Langerhans consist of different cells, the alpha cells, beta cells and other cells that produce the hormones. The alpha cells, for example, produce glucagon, the beta cells insulin. Alongside insulin, glucagon is a very important hormone for carbohydrate metabolism. It has largely opposite effects to insulin on carbohydrate, protein and fatty acid metabolism and is the most important insulin antagonist. It serves to provide energy-rich substances (primarily glucose) with the aim of keeping blood sugar levels constant and mobilizing energy reserves. ⁽¹⁾

In type 1 diabetes, previously unknown mechanisms lead to the activation of autoreactive T lymphocytes, later also B lymphocytes and the formation of autoantibodies, which induce an inflammatory reaction of the pancreas (insulitis). The beta cells are destroyed.⁽²⁾ In type 1 diabetes, the counter-regulatory glucagon response to low plasma glucose is impaired. The resulting increased risk of hypoglycemia requires new strategies to alleviate the impairment of alpha cells.

Using their type 1 diabetes-like in vitro model, the team of scientists mimicked alpha cell damage by first establishing human islet microtissue exposed to proinflammatory cytokines. They then investigated the therapeutic potential of incretin receptor agonists to improve the response of alpha cells to low blood glucose.

They were able to show that after six days of cytokine exposure, alpha cells were impaired, treatment with the substance [d-Ala2]-GIP with or without liraglutide was able to partially restore them.

Original publication:
Henriksen, K., Rufer, C., Title, A.C. et al. Proinflammatory cytokine-induced alpha cell impairment in human islet microtissues is partially restored by dual incretin receptor agonism. Diabetologia (2025). https://doi.org/10.1007/s00125-025-06425-3

Additional information:
⁽¹⁾ https://viamedici.thieme.de/
⁽²⁾ https://www.aerzteblatt.de/