Abstract
Elevated level of glucolipotoxicity induces the loss of pancreatic β-cells functions and plays an important role in the development of type 2 diabetes (T2DM). Previous studies have indicated the importance of developing therapies against T2DM, while circular RNA (circRNA) has gained attraction as a modulator of pancreatic β-cell function. In the present study role of circPIP5K1A in dysfunctional β cells and mouse pancreas was comprehensively analyzed. INS-1E, as it has close similarity with naïve pancreatic β-cells, and clinical samples of T2DM patients were used to investigate the effect of circPIP5K1A, miR-552-3p, and Janus kinase 1 (JAK1). While, INS-1E cells were exposed to PAHG conditions (0.5 mM palmitic acid and 28 mM glucose) as studies have suggested that increased level of fatty acid and glucose resulted in autophagy activation of pancreatic β-cells that leads to T2DM. Key player of JAK1-STAT3 pathway and the level of Reactive Oxygen Species, inflammatory factors, and insulin secretion was detected to analyze the of the active association of circPIP5K1A, miR-552-3p with JAK1pathway. Our study has revealed the elevated level ofcircPIP5K1A and JAK1, but reduced level of miR-552-3pin the serum of T2DM patients. Furthermore, we also found that reduced expression ofcircPIP5K1A leads to decreased rate of inflammation, oxidative damage and apoptosisinINS-1E cells induced by glucolipotoxicity. CircPIP5K1A was available to competitively combine with miR-552-3p, while whose direct target was JAK1. In conclusion, our study suggested a novel involvement of circPIP5K1A in a cross talk between miR5523p/JAK1/STAT3 pathways in β-cells as a new therapeutic target for T2DM.