P

P

P

P

P

P

P

P

P

GlycogenSynthaseGlycogenSynthase

c-Jun

EEF2K

eIF4

EEF2

TranslationAnti-apoptosis

Gene Expression

Translation

Fatty AcidSynthesis

ATP

C

itrat

e ly

ase

Glucose

EBSEBS

GeneExpression

GeneExpression

P

P

p70S6K

JNK

eIF4EBP Insulin Degradatio

n

& Receptor

Dephosphorylation

Insulin Degradatio

n

& Receptor

Dephosphorylation H+H+

eIF2B

BAD

14-3-3

BAD

MEKs

ERKs

PKC

P

PP

PAPS

c-CbI

PPtase1

GSK3

Nck

IRS1

SHCP

P

PCrk

SOS

GTP

mTOR

FKHRL1

Lipid RaftLipid Raft

Flotillin

RasCAP

GLUT4Translocation

TRETRE

GRB10

INSULININSULIN

Receptor

Internalizatio

n

Receptor

Internalizatio

n

Elk

c-Fos

InsulinReceptorInsulin

Receptor

PIP3 PIP2

AktPKB

H+

EAI

EAIInsulinInsulin

S6

Rac

PI3K

PDK

GLUT4GLUT4

GRB2

Fyn

lnsulin Receptor Pathway

RafGLUT4VesicleGLUT4Vesicle

c-CbI

InsulinInsulin

P

SHCIRS1/2

PIP2

PIP3

Rab4

P

P

P

P

P

P

P

P

P

GlycogenSynthaseGlycogenSynthase

c-Jun

TranslationAnti-apoptosisGene ExpressionTranslationFatty AcidSynthesis

Glucose

GeneExpression

GeneExpression

JNK

Insulin Degradatio

n

& Receptor

Dephosphorylation

Insulin Degradatio

n

& Receptor

Dephosphorylation H+H+

PKC

P

PP

P

APS

c-CbI

Nck

IRS1

SHCP

P

P Crk

Lipid RaftLipid Raft

Flotillin

CAPGLUT4

Translocation

TRETRE

INSULININSULIN

Receptor

Internalizatio

n

Receptor

Internalizatio

n

c-Fos

InsulinReceptorInsulin

Receptor

PIP3 PIP2

H+

EAI

EAIInsulinInsulin

Rac

PI3K

GLUT4GLUT4

GRB2

Fyn

lnsulin Receptor Pathway.A SIMPLIFIED VERSION

GLUT4VesicleGLUT4Vesicle

c-CbI

InsulinInsulin

P

SHCIRS1/2

PIP2

PIP3

Rab4

Cell membrane

Nucleus