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Abstract Autophagy is a well-preserved mechanism essential in minimizing endoplasmic reticulum stress (ER)-related cell death. Defects in β-cell autophagy have been linked to type 1diabetes, particularly deficits in the secretion of insulin, boosting ER stress sensitivity and possibly promoting pancreatic β-cell death. Quercetin (QU) is a potent antioxidant and anti-diabetic flavonoid with low bioavailability, and the precise mechanism of its anti-diabetic activity is still unknown. This study aimed to design an improved bioavailable form of QU (liposomes) and examine the impact of its treatment on the alleviation of streptozotocin (STZ)-induced type 1 diabetes in rats. Rats were divided into five groups: control, STZ, STZ+3-MA, STZ+QU-Lip, and STZ+3-MA+QU-Lip. QU-Lip significantly decreased glucose levels, oxidative, and inflammatory markers in the pancreas. It also significantly downregulated the expression of ER stress and upregulated autophagic-related markers. Furthermore, QU-Lip significantly ameliorated the expression of several MicroRNAs, which both control autophagy and ER stress signaling pathways. However, the improvement of STZ-diabetic rats was abolished upon combination with an autophagy inhibitor (3-MA). The findings suggest that QU-Lip has therapeutic promise in treating type 1 diabetes by modulating ER stress and autophagy via an epigenetic mechanism. This study was carried out to investigate the ameliorative effect of liposomal quercetin in the recovery of pancreatic beta cells and its role in acceleration of autophagal pathway in STZ-induced T1DM in adult male Sprague Dawley rats, focusing on Endoplasmic reticlum stress and autophagy pathway and its epigenetic regulation through miRNA through the following, Determination of blood glucose, C- peptide and serum insulin, Determination of oxidant- antioxidant state (MDA &SOD, GPX and CAT) in pancreatic tissue, Determination of inflammatory cytokines in pancreatic tissue (TNF-α and IL-6), Real time-PCR analysis for the gene expression of Endoplasmic reticlum Stress markers (EIF-2, ATF-6 ,CHOP , JNK , BIP , XBP-1) ,and autophagy markers. |