A proposed lectin‐mediated mechanism to explain the in Vivo antihyperglycemic activity of γ‐conglutin from Lupinus albus seeds

• Autor(a) principal: Grácio, Madalena
• Data de Publicação: 2021
• Outros Autores: Rocha, João, Pinto, Rui, Boavida Ferreira, Ricardo, Solas, João, Eduardo‐Figueira, Maria, Sepodes, Bruno, Ribeiro, Ana Cristina
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.21/13866
• topic: Diabetes mellitus type 2; Hypoglycemic activity; Insulin receptors; Lectins; Gamma-conglutin

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 the binding of γ-conglutin in the 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-conglutinates display an 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).