title: 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.
abstract: We have investigated the potential use of β-conglutin protein isoforms from narrow-leafed lupin (Lupinus angustifolius L.) as a diabetes treatment.
  
  
  
  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 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 β1, β3, and β6 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-1β) and proteins compared to healthy controls. The β2 and β4 isoforms had no effect on the insulin signaling pathway. However, these β-conglutin proteins elicited pro-inflammatory effects since levels of mRNA and proteins of inducible nitric oxide synthase and IL 1 beta were increased.
  
  
  
  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.
authors.affiliation: Plant Reproductive Biology Laboratory; Deptartment of Biochemistry, Cell & Molecular Biology of Plants, Estacion Experimental del Zaidin, Spanish National Research Council (CSIC), Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Lima-Cabello
authors.affiliation: Andalusian Health System, Health Center "Villanueva de las Torres", Granada, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Alche
authors.affiliation: The Commonwealth Scientific and Industrial Research Organisation (CSIRO), Agriculture and Food, Centre for Environment and Life Sciences (CELS); Floreat, WA, Australia.
authors.forename: Rhonda C
authors.initials: RC
authors.lastname: Foley
authors.affiliation: Department of Medicine, Heidelberg Repatriation Hospital, The University of Melbourne, Heidelberg West, VIC, Australia.
authors.forename: Sofianos
authors.initials: S
authors.lastname: Andrikopoulos
authors.affiliation: Harry Perkins Institute of Medical Research, Centre for Diabetes Research, The University of Western Australia, Perth, WA, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.affiliation: The Commonwealth Scientific and Industrial Research Organisation (CSIRO), Agriculture and Food, Centre for Environment and Life Sciences (CELS); Floreat, WA, Australia.|The UWA Institute of Agriculture, The University of Western Australia, Perth, WA, Australia.
authors.forename: Karam B
authors.initials: KB
authors.lastname: Singh
authors.affiliation: Plant Reproductive Biology Laboratory; Deptartment of Biochemistry, Cell & Molecular Biology of Plants, Estacion Experimental del Zaidin, Spanish National Research Council (CSIC), Granada, Spain.
authors.forename: Juan D
authors.initials: JD
authors.lastname: Alche
authors.affiliation: Plant Reproductive Biology Laboratory; Deptartment of Biochemistry, Cell & Molecular Biology of Plants, Estacion Experimental del Zaidin, Spanish National Research Council (CSIC), Granada, Spain.|The UWA Institute of Agriculture, The University of Western Australia, Perth, WA, Australia.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Jimenez-Lopez
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D031297:Lupinus / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry; D055314:Seed Storage Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; C508585:IL1B protein, human; D007328:Insulin; D053583:Interleukin-1beta; D055314:Seed Storage Proteins; C042457:conglutin protein, Lupinus angustifolius; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D058539:Phosphatidylinositol 3-Kinase
keywords: Anti-inflammatory; Antioxidant; GLUT-4; IL-1β; Legumes; PI3-kinase; Sweet lupins; Type 2 diabetes; Vicilin