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

Abstract

Scope: We have investigated the potential use of beta-conglutin protein isoforms from narrow-leafed lupin (Lupinus angustifolius L.) as a diabetes treatment.Methods and results: We produced purified recombinant beta 1-, beta 2-, beta 3-, beta 4-, and beta 6-conglutinproteins and showed that beta 1, beta 3, and beta 6 could bind to insulin. To assess beta-conglutin proteins modulatory effect on insulin activation meditated kinases, whole blood and peripheral blood mononuclear cell cultures from type 2 diabetes (T2D) and healthy control subjects (C) were incubated with conglutin proteins. The treatment of peripheral blood mononuclear cells from T2D patients with beta 1, beta 3, and beta 6 proteins increased up to threefold mRNA and protein levels of genes important in insulin signaling pathways, namely insulin receptor substrate 1/p85/AKT/glucose transporter type 4. This was accompanied by a comparable fold-change decrease in the mRNA expression level of pro-inflammatory genes (iNOS and IL-1 beta) and proteins compared to healthy controls. The beta 2 and beta 4 isoforms had no effect on the insulin signaling pathway. However, these beta-conglutin proteins elicited pro-inflammatory effects since levels of mRNA and proteins of inducible nitric oxide synthase and IL 1 beta were increased.Conclusion: Our results raise the possibility of using these particular beta-conglutin proteins in the prevention and treatment of diabetes, as well as their potential as anti-inflammatory molecules.