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dc.contributor.authorWartchow, Krista Minéiapt_BR
dc.contributor.authorRodrigues, Letíciapt_BR
dc.contributor.authorSuardi, Lucas Zinganopt_BR
dc.contributor.authorFederhen, Bárbara Carolinapt_BR
dc.contributor.authorSelistre, Nicholas Guerinipt_BR
dc.contributor.authorGoncalves, Carlos Alberto Saraivapt_BR
dc.contributor.authorSesterheim, Patríciapt_BR
dc.date.accessioned2021-02-24T04:17:36Zpt_BR
dc.date.issued2019pt_BR
dc.identifier.issn1422-0067pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/218161pt_BR
dc.description.abstractStudies using mesenchymal stromal cells (MSCs) as a source of insulin-secreting cells (IPCs) are a promising path in the pursuit for diabetes therapy. Here, we investigate three short-term differentiation protocols in order to generate IPCs from autologous adipose-derived stromal cells (ADSCs) with an expressive insulin-secreting profile in vitro and in vivo, as well as the signaling pathways involved in the chosen differentiation protocols. We extracted and cultured ADSCs and differentiated them into IPCs, using three different protocols with different inductors. Afterwards, the secretory profile was analyzed and IPCs differentiated in exendin-4/activin A medium, which presented the best secretory profile, was implanted in the kidney subcapsular region of diabetic rats. All protocols induced the differentiation, but media supplemented with exendin-4/activin A or resveratrol induced the expression and secretion of insulin more efficiently, and only the exendin-4/activin-A-supplemented medium generated an insulin secretion profile more like β-cells, in response to glucose. The PI3K/Akt pathway seems to play a negative role in IPC differentiation; however, the differentiation of ADSCs with exendin-4/activin A positively modulated the p38/MAPK pathway. Resveratrol medium activated the Jak/STAT3 pathway and generated IPCs apparently less sensitive to insulin and insulin-like receptors. Finally, the implant of IPCs with the best secretory behavior caused a decrease in hyperglycemia after one-week implantation in diabetic rats. Our data provide further information regarding the generation of IPCs from ADSCs and strengthen evidence to support the use of MSCs in regenerative medicine, specially the use of exendin-4/activin A to produce rapid and effectively IPCs with significant in vivo effects.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.relation.ispartofInternational journal of molecular sciences. Basel. Vol. 20, no. 10 (May 2019), 2458, 18 p.pt_BR
dc.rightsOpen Accessen
dc.subjectCélulas-tronco mesenquimaispt_BR
dc.subjectAdipose-derived stromal cellsen
dc.subjectInsulinapt_BR
dc.subjectExendin-4en
dc.subjectDiabetic ratsen
dc.subjectExenatidapt_BR
dc.subjectFosfatidilinositol 3-quinasept_BR
dc.subjectInsulin-producing cellsen
dc.subjectProteínas quinases p38 ativadas por mitógenopt_BR
dc.subjectP38-MAPKen
dc.subjectDiabetes mellitus experimentalpt_BR
dc.subjectPI3K/Akten
dc.titleShort-term protocols to obtain insulin-producing cells from rat adipose tissue : signaling pathways and in vivo effectpt_BR
dc.typeArtigo de periódicopt_BR
dc.identifier.nrb001121381pt_BR
dc.type.originEstrangeiropt_BR


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