Loss of Egr-1 sensitizes pancreatic β-cells to palmitate-induced ER stress and apoptosis

摘要: Pancreatic β-cells are particularly susceptible to fatty-acid-induced endoplasmic reticulum (ER) stress and apoptosis. To understand how sense fatty acid stimuli translate into a long-term adaptive response, we investigated whether palmitic (PA) regulates early growth response-1 (Egr-1), an immediate-early transcription factor, which is induced by many environmental implicated in cell proliferation, differentiation, We found that Egr-1 was rapidly transiently PA MIN6 insulinoma cells, accompanied calcium influx ERK1/2 phosphorylation. Calcium chelation MEK1/2 inhibition blocked PA-induced upregulation, suggesting induces expression through influx-MEK1/2-ERK1/2 cascade. Knockdown of increased caspase-3 activation ER markers decreased Akt phosphorylation insulin secretion signaling. replenishment supplementation rescued apoptosis knockdown cells. These results suggest the absence loses its ability couple short-term insulin/Akt pathway survival adaptation. Finally, Egr-1-deficient mouse islets more ex vivo In human pancreatic tissues, EGR1 correlated with anti-apoptotic gene. conclusion, further attempts rescue from improving Our study underscores as critical sensor cellular adaptation mechanism.