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

Author:

Vong Chi Teng12ORCID,Tan Dechao12ORCID,Liao Fengyun12ORCID,Chen Zhejie3ORCID,Chen Zhangmei12ORCID,Tseng Hisa Hui Ling2ORCID,Cheang Wai San2ORCID,Wang Shengpeng12ORCID,Wang Yitao12ORCID

Affiliation:

1. Macau Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, P. R. China

2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, P. R. China

3. Institute of Molecular Medicine, Shanghai Key Laboratory for Nuclei Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P. R. China

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.

Funder

Applied Basic Research Projects of Guangdong Province of China

Science and Technology Development Fund of Macau

University of Macau

Two-Way Exchange Project for Youth Talents from Guangdong and Macau, China

Publisher

World Scientific Pub Co Pte Ltd

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