Ginsenoside Rk1 Ameliorates ER Stress-Induced Apoptosis through Directly Activating IGF-1R in Mouse Pancreatic β-Cells and Diabetic Pancreas.

COMPUTER-assisted molecular modeling; PROTEIN kinases; PHOSPHOLIPIDS; RESEARCH funding; ENDOPLASMIC reticulum; APOPTOSIS; PANCREATIC beta cells; ENZYME-linked immunosorbent assay; OXIDATIVE stress; DESCRIPTIVE statistics; CELLULAR signal transduction; PANCREAS; CELL lines; MICE; GENE expression; GLYCOSIDES; TYPE 2 diabetes; ANIMAL experimentation; WESTERN immunoblotting; ONE-way analysis of variance; MOLECULAR structure; CELL receptors; CONNECTIVE tissue growth factor; CASPASES; IMMUNOBLOTTING

Hyperglycemia induces chronic stresses, such as oxidative stress and endoplasmic reticulum (ER) stress, which can result in β -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 β -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 β -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. [ABSTRACT FROM AUTHOR]

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