IGF-1 ameliorates streptozotocin-induced pancreatic β cell dysfunction and apoptosis via activating IRS1/PI3K/Akt/FOXO1 pathway

Background and objective Type 2 diabetes mellitus (T2DM) is an endocrine disorder with pancreatic beta cell dysfunction and/or reduced insulin sensitivity. IGF-1 is critically involved in pancreatic beta cell growth, differentiation, and insulin secretion. Insulin-mediated IRS1/PI3K/Akt/FOXO1 signaling has been proved to be closely associated with pancreatic beta 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 beta 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 beta 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 beta cells, induce insulin secretion, alleviate oxidative damage, as well as arrest glycolysis by activating IRS1/PI3K/Akt/FOXO1 pathway.

Automated summary

In this study, it was demonstrated that IGF-1 could protect pancreatic beta cells treated with STZ by enhancing cell viability, suppressing apoptosis, increasing insulin secretion, reducing oxidative damage, and inhibiting glycolysis. These effects may be achieved through the activation of the IRS1/PI3K/Akt/FOXO1 pathway.