In Vivo Drug Discovery For Increasing Incretinexpressing Cells In Diabetes
The new study, published in the journal Cell Chemical Biology, describes an alternative approach to treating diabetes that involves looking for drugs that directly increase the cells that express the incretin. The results of the work of Karolinska Institutet researchers.
"We have already performed an unbiased screening of small molecules for potential new diabetes treatments targeting insulin-producing beta cells. However, I think the most interesting thing about this work is that we used our unique drug discovery approach . in vivo. Various organs and enteroendocrine cells that can also improve diabetes management," explains lead researcher Olv Andersson of the Department of Cellular and Molecular Biology.
Hormones secreted by the gut play an important role in regulating satiety, insulin secretion and blood sugar levels. In terms of diabetes, incretins are hormones that are released during meals to increase insulin secretion and lower blood sugar levels. There are two different incretins called GIP and GLP-1. To identify small molecules that directly increase the number of incretin-expressing cells, the researchers created a high-throughput chemical screen in vivo by measuring the amount of GIP in zebrafish. Some of the identified drug candidates increase incretin-expressing cells and improve glucose control in zebrafish and diabetic mice.
Developing therapies that increase the number of enteroendocrine cells, rather than using hormone analogs, is an interesting approach because hormones can be physiologically secreted. Furthermore, in this study, researchers exploit the potential of zebrafish screening and present the concept that small molecules can significantly improve the enteroendocrine system, with possible implications for metabolic diseases.
To identify small molecules that increase the number of incretin-expressing cells, the researchers created a high-throughput in vivo chemical screen using the Zip promoter to drive luciferase expression in zebrafish. The zebrafish model is ideal for in vivo drug discovery, combining the high productivity of in vitro screening with the physiological complexity and relevance of animal research. They identified several findings, including one that was particularly effective in growing incretin-expressing cells in zebrafish and mice.
The researchers will now go on to test whether the findings also work in human intestinal organoids (a type of mini-organ that can be grown in cell culture). Additionally, future studies could be extended to investigate insulin secretion, incretin effects, various mouse models of diabetes, tissue-specific mutagenesis, and human cell/tissue studies. In general, increasing the number of enteroendocrine cells is an area of research that has yet to be explored therapeutically.
Further information: Lianhe Chu et al, In Vivo Drug Discovery of Incretin-Expressing Cells Identifies DYRK Inhibitors that Enhance the Enteroendocrine System, Cell Chemistry Biology (2022). DOI: 10.1016 / j.chembiol.2022.08.001Citation: In vivo discovery of drugs to stimulate incretin-expressing cells in diabetes (23 Aug 2022). Retrieved September 4, 2022, from https://phys.org/news/2022-08-vivo-drug-discovery-incretin-expressing. -cells.html
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