Table 1 The gene interactions incorporated into the model with reference to the existing literature
From: Boolean network modeling of β-cell apoptosis and insulin resistance in type 2 diabetes mellitus
Gene interations | Reference |
|---|---|
IRE1 ↑→ XBP1 ↑→β-cell dysfunction | [26] |
(IRE1 + TRAF2 + ASK1) ↑→ JNK ↑→ BCL2 (anti-apoptotic gene) ↓ | |
BCL2 ↓→ (BAX + BAK) (pro-apoptotic) ↑ | |
PERK ↑→ EIF2S1 ↓→ ATF4 ↑→ CHOP (pro-apoptotic) ↑ | [27] |
ATF6 ↑→ CHOP (pro-apoptotic) ↑→ BCL2 (anti-apoptotic gene) ↓ | |
Oxidative stress ↑→ ASK1 ↑, JNK ↑, p38 ↑ | |
p38 ↑→ CHOP (pro-apoptotic) ↑ | [34] |
FasL ↑→ (FasR + FADD + pro-caspase-8) ↑→ caspase-8 ↑→ caspase-3 ↑→ apoptosis | [53] |
TNF α↑→ (TNFR1 + TRADD) ↑→ RIPK1 ↑, FADD ↑, TRAF2 ↑ | [54] |
FADD ↑→ caspase-8 ↑ | [54] |
RIPK1 ↑→ RAIDD ↑→ caspase-8 ↑ | [54] |
TNF α↑→ TNFR2 TNF α↑→ TRAF2 ↑→...→ JNK ↑, NF-kB ↑ | |
(BAX + BAK) (pro-apoptotic) ↑→ Cytochrome c ↑→ (APAF1 + caspase-9) ↑→ caspase-3 ↑ | |
XIAP ↑→ caspase-3 ↓, caspase-7 ↓, caspase-9 ↓ | |
DIABLO ↑, HtrA2 ↑→ XIAP ↓ | [37] |
INSR ↑→ IRS ↑→ PI3K ↑→... → AKT ↑→ FOXO1 ↓, GSK3 β↓, GLUT4 ↑ | |
GSK3 β↑→ GS ↓→ glycogen synthesis ↓ | |
FOXO1 ↑→ PEPCK ↑, G6PC ↑→ glucose synthesis ↑ | |
(mTORC1 + S6K) ↑→ IRS ↓ | |
IKK β↑→ TSC1/2 ↓→ mTORC1 ↑ | [62] |
ER stress ↑→... → IRE1 ↑→... → JNK ↑→ IRS ↓ | |
ER stress ↑→... → IRE1 ↑→ XBP1 ↑→ FOXO1 ↓ | [64] |
PERK ↑→ FOXO1 ↑ | [65] |
ER stress ↑→... → ATF4 ↑→ CHOP ↑→ TRB3 ↑→ AKT ↓ | |
IL-6 ↑→ JAK ↑→ STAT3 ↑→ SOCS3 ↑→ IRS ↓ |