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

Elena Lima-Cabello, Victor Alche, Rhonda C. Foley, Sofianos Andrikopoulos, Grant Morahan, Karam B. Singh, Juan D. Alche, Jose C. Jimenez-Lopez
2017 Molecular Nutrition & Food Research  
Scope: We have investigated the potential use of -conglutin protein isoforms from narrowleafed lupin (Lupinus angustifolius L.) as a diabetes treatment. Methods and results: We produced purified recombinant 1-, 2-, 3-, 4-, and 6conglutin proteins and showed that 1, 3 and 6 could bind to insulin. To assess -conglutin proteins modulatory effect on insulin-activation meditated kinases, whole blood and peripheral blood mononuclear cell (PBMC) cultures from Type 2 diabetes (T2D) and
more » ... control subjects (C) were incubated with conglutin proteins. Treatment of PBMCs from T2D patients with 1, 3, and 6 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 proinflammatory genes (iNOS and IL-1) and proteins compared to healthy controls. The 2 and 4 isoforms had no effect on the insulin signalling pathway. However, these -conglutin proteins elicited pro-inflammatory effects since levels of mRNA and proteins of iNOS and IL-1 were increased. Conclusion: Our results raise the possibility of using these particular -conglutin proteins in the prevention and treatment of diabetes, as well as their potential as anti-inflammatory molecules. INTRODUCTION Recently, the health beneficial effects of plant-derived compounds have been increasingly investigated [1], including proteins from legume seeds [2], as food supplements [3]. These studies showed the biological activities of some legume proteins and proteins from other plant species as modulaters of chronic diseases [4, 5]. However, most of these studies did not investigate the molecular mechanisms underlying these positive health effects. Furthermore, most studies used whole seeds, where thousands of compounds would be present, and thereby not defining the exact molecule(s) that promote particular health effects such as reduction of body weight, food intake [6], and a decrease in the LDL level in plasma [7]. Considerable interest has been focused towards legume seed proteins [8], especially those from lupins, a legume of the Fabaceae family. The seeds of the "Sweet Lupins" (Lupinus angustifolius or blue lupin; Lupinus albus or white lupin; and Lupinus luteus or yellow lupin) have low alkaloid content [9], and are attracting attention because of their nutritional attributes [10] and potential for disease improvement [11]. These properties are associated with the seeds' high protein, dietary fiber content, which help reduce blood pressure and the risk of cardiovascular disease [12], as well as impacting on the prevention and treatment of Type 2 diabetes (T2D) [13]. The question that needs to be answered is which compound(s) among the lupin seed content mediates these effects. Narrow-leafed lupin (NLL), Lupinus angustifolius (L.) seeds are rich in proteins, which belong to four main families: α, , γ, and δ conglutins [14]. Of these, the β conglutins, a vicilin or 7S globulin, is the major seed storage protein in NLL and in Lupinus species [15], which belong to the Cupin superfamily [16], and mainly associated (as storage protein funtion) with plant physiological proccesses through the supply of aminoacids during seedling germination [17]. NLL seed storage proteins are getting increased awareness and international recognition as a potential food for humans as its protein-rich seeds contain a
doi:10.1002/mnfr.201600819 pmid:28012244 fatcat:wfssvvcvqffzha2xgb4utjksja