Astragalus polysaccharide ameliorates insulin resistance in HepG2 cells through activating the STAT5/IGF-1 pathway

by Selleckchem | Jan 21 2024

Background: Insulin resistance (IR) is considered as a major factor initiating type 2 diabetes mellitus and can lead to a reduction in glucose uptake that mainly occurs in the liver. Astragalus polysaccharide (APC), extracted from the traditional Chinese medicine, has been recorded to suppress IR. However, the underlying mechanism remains inadequately explored.

Methods: IR was induced in HepG2 cells which further underwent APC treatment. Cell viability was determined by cell counting kit-8 assay. Pretreatment with AG490, an inhibitor of signal transducer and activator of transcription 5 (STAT5) signaling, was performed for investigating the influence of STAT5 on APC. Glucose uptake level was reflected by 2-deoxyglucose-6-phosphate content determined through colorimetric assay. Expression levels of insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), phosphorylated-STAT5/STAT5, and p-protein kinase B (AKT)/AKT in the cells were assessed by Western blot. Radioimmunoassay (RIA) was used to detect IGF-1 secretion in the cells.

Results: APC at doses of 10 and 20 mg increased the viability of HepG2 cells with/without IR induction, and abrogated IR-induced inhibition of glucose intake. Meanwhile, APC (10 mg) offset IR-induced inhibition on the expressions of IGF-1R and IGF-1, the activation of AKT and STAT5, and the secretion of IGF-1 in HepG2 cells. More importantly, the reversal effect of APC on IR-induced alterations in HepG2 cells was counteracted by AG490.

Conclusion: APC ameliorates IR in HepG2 cells through activating the STAT5/IGF-1 pathway.

Comments:

The study you've outlined delves into the potential mechanisms by which Astragalus polysaccharide (APC), extracted from traditional Chinese medicine, may mitigate insulin resistance (IR) in HepG2 cells. The findings suggest that APC treatment positively influences cell viability and glucose uptake in these cells, particularly in the presence of IR induction. Additionally, APC appears to counteract IR-induced inhibition of insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) expression, along with activating protein kinase B (AKT) and signal transducer and activator of transcription 5 (STAT5) signaling pathways.

The crucial aspect highlighted is that APC's effects on IR in HepG2 cells seem to be mediated through the STAT5/IGF-1 pathway. This conclusion is supported by observations where the reversal effects of APC on IR-induced alterations were negated upon the inhibition of STAT5 using AG490.

The study provides a potential avenue for understanding how APC exerts its beneficial effects against IR, suggesting that APC activates STAT5, consequently modulating the expression of IGF-1 and IGF-1R and activating AKT. These findings could have implications for further research into potential therapeutic strategies targeting the STAT5/IGF-1 pathway to manage insulin resistance in the context of type 2 diabetes mellitus.