Elsevier

Redox Biology

Volume 42, June 2021, 101964
Redox Biology

Redox regulation of the insulin signalling pathway

https://doi.org/10.1016/j.redox.2021.101964Get rights and content
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Abstract

The peptide hormone insulin is a key regulator of energy metabolism, proliferation and survival. Binding of insulin to its receptor activates the PI3K/AKT signalling pathway, which mediates fundamental cellular responses. Oxidants, in particular H2O2, have been recognised as insulin-mimetics. Treatment of cells with insulin leads to increased intracellular H2O2 levels affecting the activity of downstream signalling components, thereby amplifying insulin-mediated signal transduction. Specific molecular targets of insulin-stimulated H2O2 include phosphatases and kinases, whose activity can be altered via redox modifications of critical cysteine residues. Over the past decades, several of these redox-sensitive cysteines have been identified and their impact on insulin signalling evaluated. The aim of this review is to summarise the current knowledge on the redox regulation of the insulin signalling pathway.

Keywords

H2O2
Redox regulation
ROS
Insulin signalling
Cysteine post-translational modification
FOXO
NRF2
Type-2 diabetes

Abbreviations

ARE
antioxidant response element
BCNU
bis-chloroethyl nitrosourea
EGF
endothelial growth factor
EGFR
endothelial growth factor receptor
FOXO
forkhead box class O
G6PD
glucose-6-phosphate dehydrogenase
GK
glucokinase
Grx
glutaredoxin
GSH
glutathione
GSSG
glutathione disulphide (oxidised glutathione)
GPX
glutathione peroxidase
GR
glutathione reductase
GST
glutathione S-transferase
GSK3β
glycogen synthase kinase-3β
H2O2
hydrogen peroxide
HFD
high fat diet
IGF
insulin-like growth factor
IR
insulin receptor
IRS
insulin receptor substrate
keap1
kelch-like ECH-associated protein 1
KO
knock-out
NOX
NADPH oxidase
NRF2
nuclear factor erythroid 2-related factor 2
PDK
3-phosphoinositide-dependent protein kinase
PI3K
phosphoinositide 3-kinase
PIP2
phosphatidylinositol 4,5-bisphosphate
PIP3
phosphatidylinositol 3,4,5-trisphosphate
PKB
protein kinase B (also known as AKT)
PDGF
platelet-derived growth factor
PDGFR
platelet-derived growth factor receptor
PTEN
phosphate and tensin homolog
PTM
post-translational modification
PTP
protein tyrosine phosphatase
ROS
reactive oxygen species
SOD
superoxide dismutase
SREBP
sterol regulatory element-binding protein
Trx
thioredoxin
TrxR
thioredoxin reductase
T2D
type-2 diabetes
WT
wild-type

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