Antidiabetic effects and mechanisms of action of γ-conglutin from lupin seeds

[Display omitted] •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 peptide...

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Published in:	Journal of functional foods Vol. 87; p. 104786
Main Authors:	Tapadia, Mrunmai, Johnson, Stuart, Utikar, Ranjeet, Newsholme, Philip, Carlessi, Rodrigo
Format:	Journal Article
Language:	English
Published:	Elsevier Ltd 01.12.2021
Subjects:	Antidiabetic DPP4 inhibitor gastrointestinal system glucose glycogen half life healthy diet humans insulin Insulin mimetic insulin secretion Lupin seeds Lupinus markets myotubes oral administration protein synthesis proteolysis secretin skeletal muscle value added γ-conglutin Lupin seeds OPA 2-NBDG eIF4e S6 DH KRBB DPP4 inhibitor Gαq/PLC/PKC IRS-1 Antidiabetic HSMM MTT γ-conglutin OPP AUC DPP4 BSA PI3K FBS mTOR ESI PBS pNPG GLP-1 MS IR GS ECL GIP RP-HPLC SDS-PAGE 70S6K GSK3β Insulin mimetic MWCO ERK1/2 TSC1/2 4EBPI PI PDK-1 mTORC2 GAPDH ELISA
ISSN:	1756-4646, 2214-9414
Online Access:	Get full text
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Summary:	[Display omitted] •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). 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1756-4646 2214-9414
DOI:	10.1016/j.jff.2021.104786