Lupin seed hydrolysate promotes G-protein-coupled receptor, intracellular Ca2+ and enhanced glycolytic metabolism-mediated insulin secretion from BRIN-BD11 pancreatic beta cells

Lupin seed proteins have been reported to exhibit hypoglycaemic effects in animals and humans following oral administration, however little is known about its mechanism of action. This study investigated the signalling pathway(s) responsible for the insulinotropic effect of the hydrolysate obtained...

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Published in:Molecular and cellular endocrinology Vol. 480; pp. 83 - 96
Main Authors: Tapadia, Mrunmai, Carlessi, Rodrigo, Johnson, Stuart, Utikar, Ranjeet, Newsholme, Philip
Format: Journal Article
Language:English
Published: Elsevier B.V 15.01.2019
Subjects:
adenosine triphosphate
calcium
digestive enzymes
dose response
functional foods
G-protein coupled receptors
glucose
glycemic effect
glycolysis
Gαq protein
humans
hydrolysates
Hypoglycaemic
insulin secretion
Insulinotropic
islets of Langerhans
Lupin
Lupinus angustifolius
mechanism of action
noninsulin-dependent diabetes mellitus
Nutraceutical
oral administration
phospholipase C
potassium channels
potassium chloride
protein kinase C
seed extracts
signal transduction
β-Cells
OPA
2-NBDG
GTP
DH
KRBB
DMSO
PLC
E:Ex
FCCP
cAMP
K-ATP
RIPA
phosphatidylinositol 4
GDP
CREB
FSC
SSC
AC
Hypoglycaemic
GLP-1
β-Cells
Nutraceutical
T2D
PKA
TBST
Lupin
PKC
DAG
IP3
ECAR
SEC
MWCO
Insulinotropic
EPAC2
CRE
GSIS
AMPK
GPCR
PI
Gαq protein
OCR
GLP-1R
MCT
ISSN:0303-7207, 1872-8057, 1872-8057
Online Access:Get full text
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Summary:Lupin seed proteins have been reported to exhibit hypoglycaemic effects in animals and humans following oral administration, however little is known about its mechanism of action. This study investigated the signalling pathway(s) responsible for the insulinotropic effect of the hydrolysate obtained from lupin (Lupinus angustifolius L.) seed extracts utilizing BRIN-BD11 β-cells. The extract was treated with digestive enzymes to give a hydrolysate rich in biomolecules ≤7 kDa. Cells exhibited hydrolysate induced dose-dependent stimulation of insulin secretion and enhanced intracellular Ca2+ and glucose metabolism. The stimulatory effect of the hydrolysate was potentiated by depolarizing concentrations of KCl and was blocked by inhibitors of the ATP sensitive K+ channel, Gαq protein, phospholipase C (PLC) and protein kinase C (PKC). These findings reveal a novel mechanism for lupin hydrolysate stimulated insulin secretion via Gαq mediated signal transduction (Gαq/PLC/PKC) in the β-cells. Thus, lupin hydrolysates may have potential for nutraceutical treatment in type 2 diabetes. •Lupin hydrolysate promotes insulin secretion in pancreatic β cells.•Mechanism involves activation of a Gαq-PLC-PKC pathway.•Hydrolysate-induced effects are glucose permissive and involves enhanced glycolysis.•Hydrolysate promotes membrane depolarisation and release of intracellular Ca2+.
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ISSN:0303-7207
1872-8057
1872-8057
DOI:10.1016/j.mce.2018.10.015