Fan Cui1, Xin He2. 1. Department of Clinical Laboratory, The First People's Hospital of Wuhu, Wuhu, 241000, Anhui Province, China. 2. Clinical Laboratory Center, The First Affiliated Hospital of Jinan University, Tianhe District, No. 613 West Huangpu Avenue, Guangzhou, 510630, Guangdong Province, China. hexin12233@163.com.
Abstract
BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is an endocrine disorder with pancreatic β cell dysfunction and/or reduced insulin sensitivity. IGF-1 is critically involved in pancreatic β cell growth, differentiation, and insulin secretion. Insulin-mediated IRS1/PI3K/Akt/FOXO1 signaling has been proved to be closely associated with pancreatic β cell function, hepatic glucose metabolism, and the development of T2DM. This present work was designed to demonstrate the protective role of IGF-1 against pancreatic β cell dysfunction and to probe into the underlying mechanisms. METHODS: Herein, cell viability, cell apoptosis, insulin secretion, oxidative stress, and glycolysis in STZ-treated INS-1 cells were measured, so as to determine the biological function of IGF-1 against pancreatic β cell dysfunction in T2DM. Additionally, whether IGF-1 could activate IRS1/PI3K/Akt/FOXO1 signaling pathway to manipulate the progression of T2DM was also investigated. RESULTS: It was discovered that IGF-1 treatment enhanced the viability and suppressed the apoptosis of STZ-treated INS-1 cells. Besides, IGF-1 treatment augmented insulin secretion of INS-1 cells in response to STZ. Moreover, IGF-1 exerted protective role against oxidative damage and displayed inhibitory effect on glycolysis in STZ-treated INS-1 cells. Mechanistically, IGF-1 treatment markedly boosted the activation of IRS1/PI3K/Akt/FOXO1 pathway. Furthermore, treatment with AG1024 (an inhibitor of IGF-1R) partially abolished the actions of IGF-1 on cell viability, cell apoptosis, insulin secretion, oxidative stress, and glycolysis in STZ-treated INS-1 cells. CONCLUSION: To conclude, IGF-1 could improve the viability and inhibit the apoptosis of STZ-treated pancreatic β cells, induce insulin secretion, alleviate oxidative damage, as well as arrest glycolysis by activating IRS1/PI3K/Akt/FOXO1 pathway.
BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is an endocrine disorder with pancreatic β cell dysfunction and/or reduced insulin sensitivity. IGF-1 is critically involved in pancreatic β cell growth, differentiation, and insulin secretion. Insulin-mediated IRS1/PI3K/Akt/FOXO1 signaling has been proved to be closely associated with pancreatic β cell function, hepatic glucose metabolism, and the development of T2DM. This present work was designed to demonstrate the protective role of IGF-1 against pancreatic β cell dysfunction and to probe into the underlying mechanisms. METHODS: Herein, cell viability, cell apoptosis, insulin secretion, oxidative stress, and glycolysis in STZ-treated INS-1 cells were measured, so as to determine the biological function of IGF-1 against pancreatic β cell dysfunction in T2DM. Additionally, whether IGF-1 could activate IRS1/PI3K/Akt/FOXO1 signaling pathway to manipulate the progression of T2DM was also investigated. RESULTS: It was discovered that IGF-1 treatment enhanced the viability and suppressed the apoptosis of STZ-treated INS-1 cells. Besides, IGF-1 treatment augmented insulin secretion of INS-1 cells in response to STZ. Moreover, IGF-1 exerted protective role against oxidative damage and displayed inhibitory effect on glycolysis in STZ-treated INS-1 cells. Mechanistically, IGF-1 treatment markedly boosted the activation of IRS1/PI3K/Akt/FOXO1 pathway. Furthermore, treatment with AG1024 (an inhibitor of IGF-1R) partially abolished the actions of IGF-1 on cell viability, cell apoptosis, insulin secretion, oxidative stress, and glycolysis in STZ-treated INS-1 cells. CONCLUSION: To conclude, IGF-1 could improve the viability and inhibit the apoptosis of STZ-treated pancreatic β cells, induce insulin secretion, alleviate oxidative damage, as well as arrest glycolysis by activating IRS1/PI3K/Akt/FOXO1 pathway.