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Xiao XH, Huang QY, Qian XL, et al. Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling. Diabetes Metab Syndr Obes. 2019;12:2325-2339doi: 10.2147/DMSO.S226055.
Xiao, X. H., Huang, Q. Y., Qian, X. L., Duan, J., Jiao, X. Q., Wu, L. Y., Huang, Q. Y., Li, J., Lai, X. N., Shi, Y. B., & Xiong, L. X. (2019). Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling. Diabetes, metabolic syndrome and obesity : targets and therapy, 122325-2339. https://doi.org/10.2147/DMSO.S226055
Xiao, Xing-Hua, et al. "Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling." Diabetes, metabolic syndrome and obesity : targets and therapy vol. 12 (2019): 2325-2339. doi: https://doi.org/10.2147/DMSO.S226055
Xiao XH, Huang QY, Qian XL, Duan J, Jiao XQ, Wu LY, Huang QY, Li J, Lai XN, Shi YB, Xiong LX. Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling. Diabetes Metab Syndr Obes. 2019 Nov 13;12:2325-2339. doi: 10.2147/DMSO.S226055. eCollection 2019. PMID: 32009808; PMCID: PMC6859340.
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Diabetes Metab Syndr Obes. 2019 Nov 13;12:2325-2339. doi: 10.2147/DMSO.S226055. eCollection 2019.

Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling.

Diabetes, metabolic syndrome and obesity : targets and therapy

Xing-Hua Xiao, Qi-Yuan Huang, Xian-Ling Qian, Jing Duan, Xue-Qiao Jiao, Long-Yuan Wu, Qing-Yun Huang, Jun Li, Xing-Ning Lai, Yu-Bo Shi, Li-Xia Xiong

Affiliations

  1. Department of Pathophysiology, Medical College, Nanchang University, Nanchang 330006, People's Republic of China.

PMID: 32009808 PMCID: PMC6859340 DOI: 10.2147/DMSO.S226055

Abstract

PURPOSE: Type 1 diabetes mellitus (T1DM) is characterized by irreversible islet β cell destruction. Accumulative evidence indicated that Cdc42 and Wnt/β-catenin signaling both play a critical role in the pathogenesis and development of T1DM. Further, bio-molecular mechanisms in adipose-derived mesenchymal stem cells (ADSCs)-derived insulin-producing cells (IPCs) remain largely unknown. Our aim was to investigate the underlying mechanism of Cdc42/Wnt/β-catenin pathway in ADSC-derived IPCs, which may provide new insights into the therapeutic strategy for T1DM patients.

METHODS: ADSC induction was accomplished with DMSO under high-glucose condition. ML141 (Cdc42 inhibitor) and Wnt-3a (Wnt signaling activator) were administered to ADSCs from day 2 until the induction finished. Morphological changes were determined by an inverted microscope. Dithizone staining was employed to evaluate the induction of ADSC-derived IPCs. qPCR and Western blotting were employed to measure the mRNA and protein expression level of islet cell development-related genes and Wnt signaling-related genes. The proliferation ability of ADSC-derived IPCs was also detected with a cell counting kit (CCK) assay. The expression and secretion of Insulin were detected with immunofluorescence test and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTS: During induction, morphological characters of ADSCs changed into spindle and round shape, and formed islet-line cell clusters, with brown dithizone-stained cytoplasm. Expression levels of islet cell development-related genes were up-regulated in ADSC-derived IPCs. Wnt-3a promoted Wnt signaling markers and islet cell development-related gene expression at mRNA and protein levels, while ML141 played a negative effect. Wnt-3a promoted ADSC-derived IPC proliferation and glucose-stimulated insulin secretion (GSIS), while ML141 played a negative effect.

CONCLUSION: Our research demonstrated that DMSO and high-glucose condition can induce ADSCs into IPCs, and Wnt signaling promotes the induction. Cdc42 may promote IPC induction, IPC proliferation and insulin secretion via Wnt/β-catenin pathway, meaning that Cdc42 may be regarded as a potential target in the treatment of T1DM.

© 2019 Xiao et al.

Keywords: ADSCs; Cdc42; IPCs; ML141; Wnt signaling; insulin

Conflict of interest statement

The authors report no conflicts of interest in this work.

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