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Ginsenoside Rk1 Ameliorates ER Stress-Induced Apoptosis through Directly Activating IGF-1R in Mouse Pancreatic β-Cells and Diabetic Pancreas.
- Source :
- American Journal of Chinese Medicine; 2024, Vol. 52 Issue 4, p1195-1211, 17p
- Publication Year :
- 2024
-
Abstract
- 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]
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0192415X
- Volume :
- 52
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- American Journal of Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 178279151
- Full Text :
- https://doi.org/10.1142/S0192415X24500484