Ginsenoside Rk1 Ameliorates ER Stress-Induced Apoptosis through Directly Activating IGF-1R in Mouse Pancreatic [Formula: see text]-Cells and Diabetic Pancreas.

The American journal of Chinese medicine Pub Date : 2024-01-01 Epub Date: 2024-05-27 DOI:10.1142/S0192415X24500484
Chi Teng Vong, Dechao Tan, Fengyun Liao, Zhejie Chen, Zhangmei Chen, Hisa Hui Ling Tseng, Wai San Cheang, Shengpeng Wang, Yitao Wang
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Abstract

Hyperglycemia induces chronic stresses, such as oxidative stress and endoplasmic reticulum (ER) stress, which can result in [Formula: see text]-cell dysfunction and development of Type 2 Diabetes Mellitus (T2DM). Ginsenoside Rk1 is a minor ginsenoside isolated from Ginseng. It has been shown to exert anti-cancer, anti-inflammatory, anti-oxidant, and neuroprotective effects; however, its effects on pancreatic cells in T2DM have never been studied. This study aims to examine the novel effects of Ginsenoside Rk1 on ER stress-induced apoptosis in a pancreatic [Formula: see text]-cell line MIN6 and HFD-induced diabetic pancreas, and their underlying mechanisms. We demonstrated that Ginsenoside Rk1 alleviated ER stress-induced apoptosis in MIN6 cells, which was accomplished by directly targeting and activating insulin-like growth factor 1 receptor (IGF-1R), thus activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/Bcl-2-associated agonist of cell death (Bad)-B-cell lymphoma-2 (Bcl-2) pathway. This pathway was also confirmed in an HFD-induced diabetic pancreas. Meanwhile, the use of the IGF-1R inhibitor PQ401 abolished this anti-apoptotic effect, confirming the role of IGF-1R in mediating anti-apoptosis effects exerted by Ginsenoside Rk1. Besides, Ginsenoside Rk1 reduced pancreas weights and increased pancreatic insulin contents, suggesting that it could protect the pancreas from HFD-induced diabetes. Taken together, our study provided novel protective effects of Ginsenoside Rk1 on ER stress-induced [Formula: see text]-cell apoptosis and HFD-induced diabetic pancreases, as well as its direct target with IGF-1R, indicating that Ginsenoside Rk1 could be a potential drug for the treatment of T2DM.

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人参皂苷 Rk1 通过直接激活小鼠胰腺 [式中:见正文] 细胞和糖尿病胰腺中的 IGF-1R 改善 ER 压力诱导的细胞凋亡。
高血糖会诱发慢性应激,如氧化应激和内质网(ER)应激,从而导致[计算公式:见正文]细胞功能障碍和 2 型糖尿病(T2DM)的发生。人参皂苷 Rk1 是一种从人参中分离出来的次要人参皂苷。它已被证明具有抗癌、抗炎、抗氧化和保护神经的作用,但它对 T2DM 患者胰腺细胞的影响却从未被研究过。本研究旨在探讨人参皂苷 Rk1 对胰腺 [公式:见正文] 细胞系 MIN6 和高密度脂蛋白胆固醇诱导的糖尿病胰腺细胞ER应激诱导凋亡的新作用及其内在机制。我们证实,人参皂苷 Rk1 可缓解 ER 应激诱导的 MIN6 细胞凋亡,这是通过直接靶向和激活胰岛素样生长因子 1 受体(IGF-1R),从而激活磷酸肌醇 3 激酶(PI3K)/蛋白激酶 B(Akt)/Bcl-2-细胞死亡相关激动剂(Bad)-B 细胞淋巴瘤-2(Bcl-2)通路实现的。这一途径也在高密度脂蛋白胆固醇诱导的糖尿病胰腺中得到了证实。同时,使用 IGF-1R 抑制剂 PQ401 可消除这种抗凋亡作用,从而证实了 IGF-1R 在人参皂苷 Rk1 抗凋亡作用中的介导作用。此外,人参皂苷Rk1还能减轻胰腺重量,增加胰岛素含量,这表明它能保护胰腺免受高氟酸诱导的糖尿病的影响。综上所述,我们的研究提供了人参皂苷Rk1对ER应激诱导的[公式:见正文]细胞凋亡和HFD诱导的糖尿病胰腺的新的保护作用,以及它与IGF-1R的直接靶向作用,表明人参皂苷Rk1可能是治疗T2DM的潜在药物。
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