AMPK-mediated autophagy modulates the inflammatory cytokine expression in intestinal epithelial cells induced by high glucose

Introduction: The homeostasis of intestinal epithelial cells (IECs) is disrupted in diabetes, leading to functional changes of the gastrointestinal tract and increasing the risk of diabetic enteropathy. Methods: The aim of this study is to explore the effect of autophagy on the expression of inflammatory factors under high glucose in vitro. The effect of glucose at different concentrations (5, 10, 30 and 50 Mm) on IEC-6 cells was analyzed. Dorsomorphin (AMPK antagonist) and GSK621 (AMPK agonist) were used to examine the relationship between the autophagy and the AMPK/ULK1 signaling pathway in IEC-6 cells. Results: Our results showed that the high glucose significantly inhibited the growth of IECs, and induced more shrinkage and necrosis of cells. Autophagy was inhibited by high glucose. Furthermore, the levels of cytokines, including IL-22, INF-γ, NOS2, and TNF-α, were significantly increased, which were positively correlated with glucose concentration. Additionally, we confirmed that Dorsomorphin down-regulated the expression of p-AMPK and autophagy protein compared with GSK621. Similar, cellular immunofluorescence also detected low autophagy expression. However, GSK621 and Rapamycin increased the level of autophagy and down-regulated the secretion of pro-inflammatory factors compared with Dorsomorphin. Conclusion: Therefore, our results demonstrate that AMPK mediated autophagy may regulate levels of inflammation in IECs and improve cell survival under high glucose.

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