A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds
Abstract 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‐conglu...
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2021
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oai:doaj.org-article:db96122a0a834eb3ae75ef048a00a6aa2021-11-04T13:06:43ZA proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds2048-717710.1002/fsn3.2520https://doaj.org/article/db96122a0a834eb3ae75ef048a00a6aa2021-11-01T00:00:00Zhttps://doi.org/10.1002/fsn3.2520https://doaj.org/toc/2048-7177Abstract 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).Madalena GrácioJoão RochaRui PintoRicardo Boavida FerreiraJoão SolasMaria Eduardo‐FigueiraBruno SepodesAna Cristina RibeiroWileyarticlediabetes mellitus type 2hypoglycemic activityinsulin receptorslectinsγ‐ConglutinNutrition. Foods and food supplyTX341-641ENFood Science & Nutrition, Vol 9, Iss 11, Pp 5980-5996 (2021) |
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DOAJ |
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DOAJ |
| language |
EN |
| topic |
diabetes mellitus type 2 hypoglycemic activity insulin receptors lectins γ‐Conglutin Nutrition. Foods and food supply TX341-641 |
| spellingShingle |
diabetes mellitus type 2 hypoglycemic activity insulin receptors lectins γ‐Conglutin Nutrition. Foods and food supply TX341-641 Madalena Grácio João Rocha Rui Pinto Ricardo Boavida Ferreira João Solas Maria Eduardo‐Figueira Bruno Sepodes Ana Cristina Ribeiro A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds |
| description |
Abstract 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 |
article |
| author |
Madalena Grácio João Rocha Rui Pinto Ricardo Boavida Ferreira João Solas Maria Eduardo‐Figueira Bruno Sepodes Ana Cristina Ribeiro |
| author_facet |
Madalena Grácio João Rocha Rui Pinto Ricardo Boavida Ferreira João Solas Maria Eduardo‐Figueira Bruno Sepodes Ana Cristina Ribeiro |
| author_sort |
Madalena Grácio |
| title |
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_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_sort |
proposed lectin‐mediated mechanism to explain the in vivo antihyperglycemic activity of γ‐conglutin from lupinus albus seeds |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/db96122a0a834eb3ae75ef048a00a6aa |
| work_keys_str_mv |
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