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

Autor: Jinli Luo, Wenqi Jin, Meiying Jin, Weiwei Pan, Shengnan Gao, Xiaohua Zhao, Xingrong Lai, Liwei Sun, Chunli Piao
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmaceutical Biology, Vol 60, Iss 1, Pp 1542-1555 (2022)
Druh dokumentu: article
ISSN: 13880209
1744-5116
1388-0209
DOI: 10.1080/13880209.2022.2107019
Popis: 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 β-cells were treated with JTTF (50, 100, 200 μg/mL). LPS was used to induce pancreatic β-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, IRE1α, p- IRE1α, ATF6, eIF2α, 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 β-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.
Databáze: Directory of Open Access Journals
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