Antidiabetic effects and mechanisms of action of γ-conglutin from lupin seeds. (December 2021)

• Record Type: Journal Article
• Authors: Tapadia, Mrunmai; Johnson, Stuart; Utikar, Ranjeet; Newsholme, Philip; Carlessi, Rodrigo
• Is Part Of: Journal of functional foods. Volume 87(2021)
• Publication Date: 2021-12
• Subjects: Lupin seeds -- γ-conglutin -- Antidiabetic -- Insulin mimetic -- DPP4 inhibitor; DPP4 dipeptidyl peptidase 4 -- ECL enhanced chemiluminescence -- ELISA enzyme-linked immunosorbent assay -- FBS fetal bovine serum -- SDS-PAGE sodium dodecyl sulphate polyacrylamide gel electrophoresis -- RP-HPLC reverse phase - high performance liquid chromatography -- AUC area under curve -- ESI electrospray ionisation -- MS mass spectrometry -- MWCO molecular weight cut off -- DH degree of hydrolysis -- OPA o-phthalaldehyde -- PBS phosphate buffer saline -- HSMM human skeletal muscle myotubes -- MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) -- KRBB Krebs ringer bicarbonate buffer -- BSA bovine serum albumin -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- 2-NBDG 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose -- PI propidium iodide -- OPP o-propargyl-puromycin -- pNPG p-nitrophenyl-β-glucopyranoside -- mTOR mammalian target of rapamycin -- S6 S6 ribosomal protein -- 70S6K 70 KDa ribosomal protein S6 kinase -- ERK1/2 extracellular signal-regulated kinase 1 and 2 -- GSK3β glycogen synthase kinase-3β -- Gαq/PLC/PKC Gαq protein/phospholipase C/protein kinase C -- IR insulin receptor -- IRS-1 insulin receptor substrate -- PI3K phosphoinositide 3-kinase (PI3K) -- PDK-1 3-phosphoinositide-dependent protein kinase 1 -- mTORC2 mTOR complex 2 -- GS glycogen synthase -- TSC1/2 tuberous sclerosis complex -- 4EBPI eukaryotic initiation factor 4E binding protein 1 -- eIF4e eukaryotic initiation factor 4E -- GLP-1 glucagon like peptide 1 -- GIP gastric inhibitory peptide; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2021.104786
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Proteolytically digested γ-conglutin from lupin possesses anti-diabetic properties. γ-conglutin peptides promote glucose uptake and glycogen synthesis in human muscle cells. γ-conglutin peptides activate AKT/mTOR/p70S6K signalling and promote protein synthesis. γ-conglutin peptides inhibit the activity of dipeptidyl peptidase 4 (DPP4). Abstract: The glucose modulating properties of lupin have been attributed to its seed protein γ-conglutin. Here we explored the antidiabetic potential of γ-conglutin purified from lupin seeds in-vitro . To mimic the effects of an orally administered supplement, purified γ-conglutin was hydrolysed by gastrointestinal proteolytic enzymes and the resulting peptides evaluated for their antidiabetic effects in pancreatic β-cells and primary human skeletal muscle myotubes. γ-conglutin peptides did not promote insulin secretion in β-cells but elicited a potent insulin-mimetic action by activating insulin signalling pathways responsible for glycogen, protein synthesis, and glucose transport into myotubes. Additionally, the peptides potently suppressed the activity of DPP4 indicating their potential to increase the half-life of incretin hormones in circulation. These results substantiate the health benefits of consuming lupin seeds as part of a healthy diet and can drive the current market for lupins from primarily stockfeed, towards value-added lupin-based food products for human consumption.