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Here, this study explores the effect of miR\u2010335\u20105p on insulin resistance and pancreatic islet \u03b2\u2010cell secretion via activation of the TGF\u03b2 signaling pathway by downregulating VASH1 expression in GDM mice. The GDM mouse model was established and mainly treated with miR\u2010335\u20105p mimic, miR\u2010335\u20105p inhibitor, si\u2010VASH1, and miR\u2010335\u20105p inhibitor\u2009+\u2009si\u2010VASH1. Oral glucose tolerance test (OGTT) was conducted to detect fasting blood glucose (FBG) fasting insulin (FINS). The OGTT was also used to calculate a homeostasis model assessment of insulin resistance (HOMA\u2010IR). A hyperglycemic clamp was performed to measure the glucose infusion rate (GIR), which estimated \u03b2\u2010cell function. Expressions of miR\u2010335\u20105p, VASH1, TGF\u2010\u03b21, and c\u2010Myc in pancreatic islet \u03b2\u2010cells were determined by RT\u2010qPCR, western blot analysis, and insulin release by ELISA. The miR\u2010335\u20105p mimic and si\u2010VASH1 groups showed elevated blood glucose levels, glucose area under the curve (GAUC), and HOMA\u2010IR, but a reduced GIR and positive expression of VASH1. Overexpression of miR\u2010335\u20105p and inhibition of VASH1 contributed to activated TGF\u03b21 pathway, higher c\u2010Myc, and lower VASH1 expressions, in addition to downregulated insulin and insulin release levels. These findings provided evidence that miR\u2010335\u20105p enhanced insulin resistance and suppressed pancreatic islet \u03b2\u2010cell secretion by inhibiting VASH1, eventually activating the TGF\u2010\u03b2 pathway in GDM mice, which provides more clinical insight on the GDM treatment.<\/jats:p>","DOI":"10.1002\/jcp.27406","type":"journal-article","created":{"date-parts":[[2018,10,20]],"date-time":"2018-10-20T10:09:41Z","timestamp":1540030181000},"page":"6654-6666","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["miR\u2010335\u20105p induces insulin resistance and pancreatic islet \u03b2\u2010cell secretion in gestational diabetes mellitus mice through VASH1\u2010mediated TGF\u2010\u03b2 signaling 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