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A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds
Experiments conducted in vitro and in vivo, as well as clinical trials for hypoglycemic therapeutics, support the hypoglycemic properties of the lectin γ‐conglutin, a Lupinus seed storage protein, by a mechanism not yet been clarified. Structural studies established that binding of γ‐conglutin, in n...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565248/ https://www.ncbi.nlm.nih.gov/pubmed/34760231 http://dx.doi.org/10.1002/fsn3.2520 |
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author | Grácio, Madalena Rocha, João Pinto, Rui Boavida Ferreira, Ricardo Solas, João Eduardo‐Figueira, Maria Sepodes, Bruno Ribeiro, Ana Cristina |
author_facet | Grácio, Madalena Rocha, João Pinto, Rui Boavida Ferreira, Ricardo Solas, João Eduardo‐Figueira, Maria Sepodes, Bruno Ribeiro, Ana Cristina |
author_sort | Grácio, Madalena |
collection | PubMed |
description | Experiments conducted in vitro and in vivo, as well as clinical trials for hypoglycemic therapeutics, support the hypoglycemic properties of the lectin γ‐conglutin, a Lupinus seed storage protein, by a mechanism not yet been clarified. Structural studies established that binding of γ‐conglutin, in native and denatured form, to insulin occurs by a strong binding that resists rupture when 0.4 M NaCl and 0.4 M galactose are present, suggesting that strong electrostatic interactions are involved. Studies on binding of γ‐conglutin in native and denatured form to HepG2 membrane glycosylated receptors were conducted, which reveal that only the native form of γ‐conglutin with lectin activity is capable of binding to these receptors. Glycosylated insulin receptors were detected on purified HepG2 cell membranes and characterized by 1D and 2D analyses. Preclinical assays with male mice (CD‐1) indicated that native and denatured γ‐conglutins display antihyperglycemic effect, decreasing glucose in blood comparable after 120 min to that exhibited by the animal group treated with metformin, used to treat T2D and used as a positive control. Measurement of organ injury/functional biomarkers (hepatic, pancreatic, renal, and lipid profile) was comparable to that of metformin treatment or even better in terms of safety endpoints (pancreatic and hepatic biomarkers). |
format | Online Article Text |
id | pubmed-8565248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85652482021-11-09 A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds Grácio, Madalena Rocha, João Pinto, Rui Boavida Ferreira, Ricardo Solas, João Eduardo‐Figueira, Maria Sepodes, Bruno Ribeiro, Ana Cristina Food Sci Nutr Original Research Experiments conducted in vitro and in vivo, as well as clinical trials for hypoglycemic therapeutics, support the hypoglycemic properties of the lectin γ‐conglutin, a Lupinus seed storage protein, by a mechanism not yet been clarified. Structural studies established that binding of γ‐conglutin, in native and denatured form, to insulin occurs by a strong binding that resists rupture when 0.4 M NaCl and 0.4 M galactose are present, suggesting that strong electrostatic interactions are involved. Studies on binding of γ‐conglutin in native and denatured form to HepG2 membrane glycosylated receptors were conducted, which reveal that only the native form of γ‐conglutin with lectin activity is capable of binding to these receptors. Glycosylated insulin receptors were detected on purified HepG2 cell membranes and characterized by 1D and 2D analyses. Preclinical assays with male mice (CD‐1) indicated that native and denatured γ‐conglutins display antihyperglycemic effect, decreasing glucose in blood comparable after 120 min to that exhibited by the animal group treated with metformin, used to treat T2D and used as a positive control. Measurement of organ injury/functional biomarkers (hepatic, pancreatic, renal, and lipid profile) was comparable to that of metformin treatment or even better in terms of safety endpoints (pancreatic and hepatic biomarkers). John Wiley and Sons Inc. 2021-09-18 /pmc/articles/PMC8565248/ /pubmed/34760231 http://dx.doi.org/10.1002/fsn3.2520 Text en © 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Grácio, Madalena Rocha, João Pinto, Rui Boavida Ferreira, Ricardo Solas, João Eduardo‐Figueira, Maria Sepodes, Bruno Ribeiro, Ana Cristina A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
title | A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
title_full | A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
title_fullStr | A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
title_full_unstemmed | A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
title_short | A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
title_sort | proposed lectin‐mediated mechanism to explain the in vivo antihyperglycemic activity of γ‐conglutin from lupinus albus seeds |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565248/ https://www.ncbi.nlm.nih.gov/pubmed/34760231 http://dx.doi.org/10.1002/fsn3.2520 |
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