Saturated fatty acids entrap PDX1 in stress granules and impede islet beta cell function – published online 11/02/2021

Mu Zhang, Chunjie Yang, Meng Zhu, Li Qian, Yan Luo, Huimin Cheng, Rong Geng, Xiaojun Xu, Cheng Qian, Yu Liu

Failure of pancreatic and duodenal homeobox factor 1 (PDX1) to localise in the nucleus of islet beta cells under high-fat-diet conditions may contribute to beta cell failure in type 2 diabetes; however, the mechanism of PDX1 intracellular mislocalisation is unclear. Saturated fatty acids (SFAs) are known to be adverse factors in blood glucose regulation, but the underlying mechanisms for this are unknown. Owing to their biochemical features, SFAs are involved in liquid–liquid phase separation, whilst stress granules (SGs) are cytoplasmic structures that form by phase separation and impair nucleocytoplasmic transport. In this issue, Zhang et al (https://doi.org/10.1007/s00125-021-05389-4) investigated whether SG formation contributes to PDX1 mislocalisation and beta cell dysfunction under SFA-induced stress conditions. They found that SGs assembled in cells after they were exposed to SFAs, and that this was dependent on the phosphoinositide 3-kinase (PI3K)/eukaryotic translation initiation factor 2α (eIF2α) axis. They also demonstrated that PDX1 was entrapped in SGs after SFA treatment. The authors suggest that modulation of SG formation may ameliorate the impairment of pancreatic beta cell function and may be a potential therapeutic strategy for obesity and type 2 diabetes.

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