Institution of Shenzhen Hospital, Guangzhou University of Chinese Medicine (Futian), Shenzhen, China.
Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
Pharm Biol. 2022 Dec;60(1):1542-1555. doi: 10.1080/13880209.2022.2107019.
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.
This study explores the potential effect of JTTF on ERS and autophagy in the pancreas.
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 Ca concentration was measured using flow cytometry, while ERS and autophagy levels were monitored via Western blotting and/or immunostaining.
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 Ca (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.
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.
解毒通络灌胃方（JTTF）是一种中药，可促进胰岛功能。然而，JTTF 对内质网应激（ERS）和自噬的潜在影响尚未报道。
本研究探讨 JTTF 对胰腺 ERS 和自噬的潜在影响。
将 Zucker 糖尿病肥胖（ZDF）大鼠随机分为五组，对照组、模型组、JTTF（1、3、5 g/kg/天，共 12 周）。用 JTTF（50、100、200μg/mL）处理 LPS 诱导的胰腺β细胞。用 LPS 诱导胰腺β细胞损伤，用 MTT、葡萄糖刺激胰岛素分泌（GSIS）测定和 PCR 评估细胞活力和胰岛素分泌。用流式细胞术测量细胞内 Ca 浓度，用 Western blot 和/或免疫染色监测 ERS 和自噬水平。
与模型组相比，JTTF 治疗组的体重、FGB、HbA1c、IPGTT、FINs 和 HOMA-IR 均显著降低。在 JTTF 处理的胰岛细胞中，JTTF 组的胰岛细胞增加，脂滴减少，Ca 降低（16.67%）。JTTF 干预后，PERK、p-PERK、IRE1α、p-IRE1α、ATF6、eIF2α、GRP78、p-ULK1、LC3 和 p62 的表达降低，而 Beclin1 和 p-mTOR 的表达增加。此外，JTTF 组的凋亡相关蛋白表达低于对照组。
JTTF 可能通过抑制糖尿病大鼠胰岛β细胞的内质网应激和过度自噬来减轻胰岛β细胞损伤。这为通过中药治疗糖尿病和恢复胰腺功能提供了新的方向。
