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文献信息

A saponin from astragalus promotes pancreatic ductal organoids differentiation into insulin-producing cells

期刊名:Phytomedicine
文献编号:
文献地址: https://www.sciencedirect.com/science/article/pii/S0944711322002689
发表日期:20 July 2022
Background

Islet transplantation is an effective treatment for the type 1 and severe type 2 diabetes, but it is restricted by the severe lack of pancreas donors. In vitro differentiation of pancreatic progenitors into insulin-secreting cells is one of the hopeful strategies in the cell transplantation therapy of diabetes. Isoastragaloside I is one of the saponin molecules found in Astragalus membranaceus, which has been demonstrated to alleviate insulin resistance and glucose intolerance in obese mice.

Study design

We established mouse pancreatic ductal organoids (mPDOs) with progenitor characteristics and an insulin promoter-driven EGFP reporter system to screen astragalus saponin components for monomers that can promote insulin-producing cell differentiation.

Methods

mPDOs treated with or without astragalus saponin monomers were investigated by the insulin promoter-driven EGFP reporter, quantitative PCR, immunofluorescence and flow cytometry to evaluate the expression of endocrine progenitor and β-cell markers.

Results

Isoastragaloside I significantly promoted the expression of β-cell differentiation genes, which was demonstrated by the activation of the insulin promoter-driven EGFP reporter, as well as the significant increase of mRNA levels of the endocrine progenitor marker Ngn3 and the β-cell markers insulin1 and insulin2. Immunostaining studies indicated that the β-cell-specific C-peptide was upregulated in isoastragaloside I-treated mPDOs. FACS analysis revealed that the ratio of C-peptide-secreting cells in isoastragaloside I-treated mPDOs was over 40%. Glucose tolerance tests demonstrated that the differentiated mPDOs could secrete C-peptide in response to glucose stimulation.

Conclusions

We discover a novel strategy of inducing pancreatic ductal progenitors to differentiate into insulin-producing cells using isoastragaloside I. This approach can be potentially applied to β-cell transplantation in diabetes therapies.
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