Ginsenoside Rk1 Ameliorates ER Stress-Induced Apoptosis through Directly Activating IGF-1R in Mouse Pancreatic [Formula: see text]-Cells and Diabetic Pancreas.
Chi Teng VongDechao TanFengyun LiaoZhejie ChenZhangmei ChenHisa Hui Ling TsengWai San CheangShengpeng WangYi-Tao WangPublished in: The American journal of Chinese medicine (2024)
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.
Keyphrases
- induced apoptosis
- oxidative stress
- signaling pathway
- diabetic rats
- endoplasmic reticulum stress
- pi k akt
- cell cycle arrest
- type diabetes
- cell death
- high glucose
- stress induced
- endoplasmic reticulum
- dna damage
- anti inflammatory
- high fat diet
- glycemic control
- ischemia reperfusion injury
- smoking cessation
- drug induced
- binding protein
- human milk
- emergency department
- protein kinase
- cardiovascular disease
- risk assessment
- human health
- mouse model
- insulin resistance
- metabolic syndrome
- diffuse large b cell lymphoma
- skeletal muscle
- mesenchymal stem cells
- heat shock
- preterm birth
- heat shock protein