1. Academic Validation
  2. A saponin from astragalus promotes pancreatic ductal organoids differentiation into insulin-producing cells

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

  • Phytomedicine. 2022 Jul 20;102:154190. doi: 10.1016/j.phymed.2022.154190.
Wen Yu 1 Yannan Wang 1 Di Jiang 1 Jie Shang 1 Miao Liu 1 Thomas Efferth 2 Chun-Bo Teng 3
Affiliations

Affiliations

  • 1 College of Life Science, Northeast Forestry University, Harbin, PR China.
  • 2 Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
  • 3 College of Life Science, Northeast Forestry University, Harbin, PR China. Electronic address: chunboteng@nefu.edu.cn.
Abstract

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.

Keywords

Astragalus saponins; Diabetes mellitus; Differentiation; Insulin-producing cells; Organoids.

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