Jiedutongluotiaogan formula restores pancreatic function by suppressing excessive autophagy and endoplasmic reticulum stress

Context: Jiedutongluotiaogan formula (JTTF), a traditional Chinese medicine (TCM), could promote islet function. However, the potential effect of JTTF on endoplasmic reticulum stress (ERS) and autophagy have not been reported. Objective: This study explores the potential effect of JTTF on ERS and autophagy in the pancreas. Materials and methods: The Zucker diabetic fatty (ZDF) rats were randomised into five groups, control, model, JTTF (1, 3, 5 g/kg/day for 12 weeks). LPS induced pancreatic (3-cells were treated with JTTF (50, 100, 200 mu g/mL). LPS was used to induce pancreatic beta-cell injury, with cell viability and insulin secretion evaluated using MTT, glucose-stimulated insulin secretion (GSIS) assays, and PCR. Intracellular Ca2+ concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining. Results: Compared with the model group, body weight, FGB, HbA1c, IPGTT, FINs, and HOMA-IR in JTTF treatment groups were significantly reduced. In islets cells treated with JTTF, the pancreatic islet cells in the JTTF group were increased, lipid droplets were reduced, and there was a decrease in Ca2+ (16.67%). After JTTF intervention, PERK, p-PERK, IRE1 alpha, p- IRE1 alpha, ATF6, elF2 alpha, GRP78, p-ULK1, LC3 and p62 expression decreased, whereas Beclin1and p-mTOR expression increased. In addition, the expression of proteins related to apoptosis in the JTTF groups were lower than those in the control group. Discussion and conclusions: JTTF may alleviate pancreatic p-cell injury by inhibiting ER stress and excessive autophagy in diabetic rats. This provides a new direction for treating diabetes and restoring pancreatic dysfunction by TCM.