Table 2.

Parameter values of the model (except for FOXO part)

Module	Reaction	Name	Parameter	Value	Order	Comments & Ref
All		Volume	extracellular	8.3 × 10-12 l		0.5 × cytoplasm
		Volume	cell surface	6.4 × 10-14 l		assumes thickness of 20 nm
		Volume	cytoplasm	1.65 × 10-11 l		typical of many cells
		Volume	nucleus	5 × 10-13 l
		Volume	DNA-bound	1 × 10-13 l
Receptor binding	R1f		k1	2.0 × 10-5	2	[36] Figure 1
m8b2_recep.6mod	R1r		kminus1	12072	1	[36]
	R2		k3	2500	1	[36]
	R3f		k2	1.2 × 10-5	2	[36]
	R3r		kminus2	9 × 104	1	> > kminus1
	R4		kminus3	2 × 10-6	2 (cat)
	R5f		k4	0.0333	1	forward/reverse ratio 10, much faster than [26]
	R5r		kminus4	0.3	1	see R5f
	R6f		k4’	0.0021	1	unchanged from [26]
	R6r		kminus4’	2.1 × 10-4	1	[26]
	R7f		k4’	0.0021	1	[26]
	R7r		kminus4’	2.1 × 10-4	1	[26]
	R10		k6	4.61 × 10-6	2 (cat)	[26] corrected for mol number of PTP1B
	R11		k6	4.61 × 10-6	2 (cat)	see R10
IRS	R12f		k7	5.8	2 (cat)	fitted to IRSYp
m8b2_irs.6.mod	R12r		kminus7a	8.75 × 10-5	2 (cat)	as R12f
	R12_a_f	IRS-SerP by PKC_P	kpsp2	2.2 × 10-4	2	changed to simple MA; [27] used for fitting
	R12_a_r		kminus7b	0.28 × 10-5	2 (cat)	as R12_a_f
	R12_b_(f,r)		as R12_a_(f,r)
	R13f		k8	2.6 × 10-6	2	[36] Figure 3
	R13r		kminus8	1.55	1	as R13f
	R50f	IRS basal synth	k_irs1_basal_syn	260	0	increased to keep IRS1 const
	R50r1	IRS degrade	k_irs_basal_degr	10-3	1	Lifetime of ~2 days
	R50r2	IRS-Yp degr	k_irs_basal_degr	10-3	1	as R50r2
	R50r3	IRS1-Sp degr	k_irs_polyserp_degr	10-2	1	10 × faster than r50r2 [43]
	R51	IRS-SerP by IKK_P	kcat51	0.87		consistent with [43] and IKK/JNK activation
		IRS-SerP by IKK_P	Km51	100		as above
	R52	IRS-SerP by JNK_P	kcat52	6.95		as R51
		IRS-SerP by JNK_P	Km52	100		as above
Phosphatases	R30f	oxidation of PTP1B	k30f	0.08	2	[18,19]
m8b2_phosph.6.mod	R30r	reduction of PTP1B by GSH	k30r	5 × 10-3	2	[18-20]
	R31f	oxidation of PTEN	k31f	2.7 × 10-4	2	slower than R30f
	R31r	reduction of PTEN by GSH	k31r	2 × 10-3	2	similar to R30r
	R34f	Activation of NOX	k34f	2 × 10-5	2	consistent with R35
	R34r1	NOX deactivation	k34r1	10-3	2	consistent with R35
	R34r2	NOX inactivation(1)	k34r2	0.25	1	consistent with R35
	R34r3	NOX deact- > inact	k34r3	10-3	2	consistent with R35
	R35f	ROS production by NOX	k35f	450	1	fitted to get desired ROS level (30/5) and PTP1B inhibition [18]
	R35r	ROS elimination by SOD2	k35r	0.12	2	lifetime < 0.01 s
	R36f	ROS production by Mitoch	k36f	180	1
	R37f, R37r	ROS transport across plasma membrane	ros_perm	7.8 × 108 (thousands cm-2min-1)	1	[35]
			membrane_area	6.5 × 10-9 cm2		from volume
			k_ros_perm	4.8 thousands min-1		product of above
	R38f	Glutathione oxidation	k38f	0.05	2	see R38f
	R38r	Glutathione reduction	k38r	2	1	(auto-reduction)
Akt	R14f	PI(3,4,5)P3 generation, basal	k9_basal	0.13145	1	[26]
m8b2_akt.6.mod		By PI3K complex	k9	0.055	2 (cat)	derived from [26]
	R14r	PIP3 breakdown, basal	kminus9_basal	2.7	1	[26]
		by PTEN	kminus9	0.0014	2 (cat)
	R16f	Akt activation	k11	2.5 × 10-5	2	modified mass action, effect similar to express in [26]
			pip3_basal	200	2 (cat)	offset
	R16r	Akt deactivation by PP2A	kminus11	1.188 × 10-6	2 (cat)	[26]
	R17f	PKC activation	k12	3.5 × 10-5	2 (cat)	as R16f
	R17r	PKC deactivation	kminus12	1.25 × 10-6	2 (cat)	as R16r
	R16a	AS160 activation by AKT	kr16a	3.33 × 10-4	2 (cat)	see methods; [26,36]
	R16r	AS160 deactivation	kminusr16a	1 × 10-6	2 (cat)	see R16a
	R20f	GLUT4 translocation to cell surface; basal	k13_basal	0.015	1	see R16a
		and by AS160	k13	7.5 × 10-6	2 (cat)	see R16a
	R20r	GLUT4 translocation to cytoplasm	kminus13	0.167	1	see R16a
JNK	R32f	DUSP oxidation	k32f	6 × 10-4	2 (cat)	consistent with [16,35,44]
m8b2_jnk.6.mod	R32r	DUSP reduction by GSH	k32r	4 × 10-4	2 (cat)	as R32f
	R42f	JNK activation by ROS	k42fa	2.5 × 10-4	2 (cat)	as R32f
	R42r	JNK deactivation by DUSP	k42r	0.5 × 10-6	2 (cat)	as R32f
	R43f	IKK activation by ROS	k43f	0.5 × 10-4	2 (cat)	as R32f
	R43r	IKK deactivation	k43r	0.5 × 10-6	2 (cat)	as R32f

^a k42f expressed as α × k42f’ where α = 5 and k42f’ = 0.5 × 10^-4.

(phosphatases, Akt, JNK, FOXO).

Kinetic parameters of the model, except for the FOXO components. Units of rate constants are min-1 for first order or (number)-1 min-1 for second order.