Isoastragaloside I improves hyperglycaemia and increases β-cell mass in mice

Aims: This study aims to investigate the effects of isoastragaloside I (IAS-I) on improving diabetic symptoms and its impact on endogenous β-cell mass, and further explore the origins of increased β-cells.

Methods: Healthy and diabetic mice received IAS-I treatment (5 or 0.5 mg/kg, respectively) via tail veil injection. The blood glycaemic control, body weight, and glucose/Insulin tolerance were evaluated. Safety was assessed via complete blood count and histopathological analysis. Uniformly sampled pancreatic sections (spanning the entire pancreas) were immunohistochemically stained for β-cells, imaged, and analysed by point-counting morphometry to estimate β-cell mass. Furthermore, SOX9-CreER^T2; R26-LSL-tdTomato mice were used to trace the pancreatic ductal cell, and conduct multiplex immunohistochemistry to explore the conversion of pancreatic ductal cells into β-cells.

Results: In both healthy and diabetic mice, IAS-I could increase the β-cell mass; especially 0.5 mg/kg IAS-I significantly increased the small islet mass. Using lineage tracing, we demonstrated that IAS-I promoted the generation of β-cells from ductal cells. We also found that IAS-I could improve the fasting blood glucose and Insulin resistance in diabetic mice, and the safety of IAS-I in vivo had also been preliminarily demonstrated.

Conclusion: Our results suggest that IAS-I increases β-cell mass and promotes the formation of β-cells from pancreatic ductal cells in vivo. It is also speculated to possess islet-protective activity. These findings provide insight into the potential application of Astragalus membranaceus monomers in diabetic treatment.

diabetes; isoastragaloside I; pancreatic ductal cell; regeneration; β cell.