Inhibition of Circular RNA 006029 Alleviates Pancreatic β-Cell Injury Through the AKT/mTOR Signaling Pathway

Introduction: Type 1 Diabetes Mellitus (T1DM) is characterized by the damage of pancreatic β-cells induced by autoimmune responses. Circular RNAs (circRNAs) play important regulatory roles in the pathogenesis of T1DM, but the underlying mechanisms require further substantiation. Method: This study focused on a novel circRNA, circ006029, to investigate its regulation on β-cell damage. The potential involvement of circ006029 in β-cell proliferation, apoptosis, autophagy, and inflammatory responses was investigated using CCK-8, qRTPCR, and immunoblot assays. The utilization of a cytokine mixture, and specific molecular blockers Rapamycin and Capivasertib, was applied to investigate the pathway by which circ006029 regulates β-cell damage. Transcriptome sequencing and bioinformatics analysis were conducted to explore differentially expressed mRNAs related to circ006029 regulation. Result: The expression of circ006029 was observed to increase in damaged MIN6 cells. The inhibition of circ006029 serves a protective role in MIN6 β-cells by promoting β-- cell proliferation and attenuating apoptosis. circ006029-knockdown could augment β-- cell autophagy and attenuate apoptosis through the AKT/mTOR signaling pathway. Moreover, circ006029 might be involved in the inflammatory response of MIN6 cells. Discussion: The knockdown of circ006029 was demonstrated to alleviate β-cell inflammation and reduce cell apoptosis. The promotion of β-cell proliferation and heightened autophagy also substantiated the protective effects of circ006029 silence. Furthermore, we also proved that circ006029 might contribute to autophagy via the AKT/mTOR signaling pathway. All the results implied that the presence of circ006029 may drive a detrimental regulatory role in pancreatic β-cells. This may provide valuable evidence that circ006029 might be a potential target for alleviating β-cell damage in T1DM and rebuilding β-cell function. Conclusion: These findings suggest that circ006029 may serve a detrimental role in β-- cell damage, which provides new ideas for exploring the mechanism of β-cell damage in early insulitis in T1DM.