The novel Angiotensin-(1-7) analog, A-1317, improves insulin resistance by restoring pancreatic β-Cell functionality in rats with metabolic syndrome.

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dc.contributor.authorBarbosa, Maria Andréa
dc.contributor.authorBarbosa, Claudiane Maria
dc.contributor.authorLima, Taynara Carolina
dc.contributor.authorSantos, Robson Augusto Souza dos
dc.contributor.authorAlzamora, Andréia Carvalho
dc.date.accessioned2021-09-23T17:37:18Z
dc.date.available2021-09-23T17:37:18Z
dc.date.issued2020pt_BR
dc.description.abstractIn previous studies we have shown that oral Ang-(1–7) has a beneficial therapeutic effect on cardiometabolic disturbances present in metabolic syndrome (MetS). Based on the fact that Ang-(1–7) acts through release of nitric oxide (NO), a new peptide, A-1317 was engineered adding the amino acid L-Arginine, the NO precursor, to the N-terminal portion of the Ang-(1– 7). Therefore, in a single molecule the substrate and the activator of NO are combined. In the present study, we evaluated the effect of A-1317 oral treatment on liver-glucose metabolism in MetS induced by high fat (HF) diet in rats. Rats were subjected to control (AIN-93M, CT) or HF diets for 15 weeks to induce MetS and treated with A-1317, Ang-(1–7) included into hydroxypropyl-b-cyclodextrin (HPbCD) or empty HPbCD (E), in the last 7 weeks. At the end of 15 weeks, hemodynamic, biometric, and biochemical parameters, redox process, and qRT-PCR gene expression of NO synthase and RAS components were evaluated in the liver. HF/E rats increased body mass gain, adiposity index, despite the reduction in food intake, increased plasma leptin, total cholesterol, triglycerides, ALT, fasting blood glucose, OGTT and insulin, HOMA-IR and MAP and HR. Furthermore, the MetS rats presented increased in liver angiotensinogen, AT1R, ACE mRNA gene expression and concentration of MDA and carbonylated protein. Both Ang-(1–7) and A-1317 oral treatment in MetS rats reverted most of these alterations. However, A-1317 was more efficient in reducing body mass gain, ALT, AST, total cholesterol, insulin, fasting blood glucose, ameliorating b cell capacity by increasing HOMA-b and QUICKI, whereas Ang-(1–7) reduced HOMA-b and QUICKI. In addition, Ang- (1–7) increased Mas and AKT liver mRNA gene expression, while A-1317 increased both Mas and MRGD and AMPK liver mRNA gene expression, suggesting a distinct pathway of action of Ang-(1–7) and A-1317 in MetS rats. Taken together, our data showed that treatment with A-1317 was able to ameliorate MetS disorders and suggested that this effect was mainly via MRGD via activation of AMPK and increasing b cell function.pt_BR
dc.identifier.citationBARBOSA, M. A. et al. The novel Angiotensin-(1-7) analog, A-1317, improves insulin resistance by restoring pancreatic β-Cell functionality in rats with metabolic syndrome. Frontiers in Pharmacology, v. 11, artigo 1263, ago. 2020. Disponível em: <https://www.frontiersin.org/articles/10.3389/fphar.2020.01263/full>. Acesso em: 10 jun. 2021.pt_BR
dc.identifier.doihttps://doi.org/10.3389/fphar.2020.01263pt_BR
dc.identifier.issn1663-9812
dc.identifier.urihttp://www.repositorio.ufop.br/jspui/handle/123456789/13798
dc.language.isoen_USpt_BR
dc.rightsabertopt_BR
dc.rights.licenseThis is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Fonte: o PDF do artigo.pt_BR
dc.subjectLiver metabolismpt_BR
dc.subjectMas-related G protein-coupled receptor member Dpt_BR
dc.subjectAdenosine monophosphate activated protein kinasept_BR
dc.titleThe novel Angiotensin-(1-7) analog, A-1317, improves insulin resistance by restoring pancreatic β-Cell functionality in rats with metabolic syndrome.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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