Narrow-leafed lupin (Lupinus angustifolius L.) β-conglutin proteins modulate the insulin signalling pathway as potential type 2 diabetes treatment and inflammatory-related disease amelioration

Abstract

SCOPE: We have investigated the potential use of β-conglutin protein isoforms from narrow-leafed lupin (Lupinus angustifolius L.) as a diabetes treatment. METHODS AND RESULTS: We produced purified recombinant β1-, β2-, β3-, β4-, and β6-conglutin proteins and showed that β1, β3 and β6 could bind to insulin. To assess β-conglutin proteins modulatory effect on insulin-activation meditated kinases, whole blood and peripheral blood mononuclear cell (PBMC) cultures from Type 2 diabetes (T2D) and healthy control subjects (C) were incubated with conglutin proteins. Treatment of PBMCs from T2D patients with β1, β3, and β6 proteins increased up to 3-folds mRNA and protein levels of genes important in insulin signalling pathways, namely IRS-1/p85 /AKT/GLUT-4. This was accompanied by a comparable fold-change decrease in the mRNA expression level of pro-inflammatory genes (iNOS and IL-1β) and proteins compared to healthy controls. The β2 and β4 isoforms had no effect on the insulin signalling pathway. However, these β-conglutin proteins elicited pro-inflammatory effects since levels of mRNA and proteins of iNOS and IL-1β were increased. CONCLUSION: Our results raise the possibility of using these particular β-conglutin proteins in the prevention and treatment of diabetes, as well as their potential as anti-inflammatory molecules.