Hu, Ruiying; Hamilton, Nala; Wang, Yu; Tong, Xin; Yagan, Mahircan; Dadi, Prasanna K.; Harmelink, Cristina; Doss, Teri D.; Liu, Jinhua; Xu, Yanwen; Simmons, Alan J.; Lau, Ken S.; Stein, Roland; Balamurugan, Appakalai N.; Kaverina, Irina; Coate, Katie C.; Jacobson, David A.; Liu, Qi; Gu, Guoqiang. (2026).听.听Diabetologia.听
This study looked at how genes and environmental stress work together to affect the beta cells in the pancreas, which make insulin and are central to type 2 diabetes. The researchers focused on a group of genes called myelin transcription factors, or MYT TFs, including MYT1 and ST18, which they had previously found help protect mouse beta cells by keeping stress responses from becoming too active. They wanted to know whether these genes also help protect human beta cells, especially under normal conditions and during obesity-related stress. To test this, they reduced MYT1 or ST18 activity in human beta cells and then examined how well the cells survived, how well they secreted insulin, and which genes changed their activity. They found that lowering MYT1 caused beta cell death, while lowering ST18 weakened the cells鈥� ability to release insulin in response to glucose, and under obesity-like stress ST18 loss also led to cell death. These changes were linked to disruptions in genes involved in stress responses, cell survival, mitochondria, and ion channels, which help cells handle electrical signals and calcium movement. The study also found that the genes controlled by MYT TFs were enriched for regions of the genome associated with type 2 diabetes. Overall, the findings suggest that MYT TFs work together to help human beta cells survive and function properly, linking both genetic risk and environmental stress to the development of type 2 diabetes.
