Table 1.

The gene interactions incorporated into the model with reference to the existing literature

Gene interations	Reference
IRE1 ↑→ XBP1 ↑→β-cell dysfunction	[26]
(IRE1 + TRAF2 + ASK1) ↑→ JNK ↑→ BCL2 (anti-apoptotic gene) ↓	[28–30]
BCL2 ↓→ (BAX + BAK) (pro-apoptotic) ↑	[50, 51]
PERK ↑→ EIF2S1 ↓→ ATF4 ↑→ CHOP (pro-apoptotic) ↑	[27]
ATF6 ↑→ CHOP (pro-apoptotic) ↑→ BCL2 (anti-apoptotic gene) ↓	[51, 52]
Oxidative stress ↑→ ASK1 ↑, JNK ↑, p38 ↑	[31–33]
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 ↑	[55–57]
(BAX + BAK) (pro-apoptotic) ↑→ Cytochrome c ↑→ (APAF1 + caspase-9) ↑→ caspase-3 ↑	[6, 58]
XIAP ↑→ caspase-3 ↓, caspase-7 ↓, caspase-9 ↓	[35, 36]
DIABLO ↑, HtrA2 ↑→ XIAP ↓	[37]
INSR ↑→ IRS ↑→ PI3K ↑→... → AKT ↑→ FOXO1 ↓, GSK3 β↓, GLUT4 ↑	[59–61]
GSK3 β↑→ GS ↓→ glycogen synthesis ↓	[42, 43]
FOXO1 ↑→ PEPCK ↑, G6PC ↑→ glucose synthesis ↑	[47, 47–49]
(mTORC1 + S6K) ↑→ IRS ↓	[44–46]
IKK β↑→ TSC1/2 ↓→ mTORC1 ↑	[62]
ER stress ↑→... → IRE1 ↑→... → JNK ↑→ IRS ↓	[38, 39, 63]
ER stress ↑→... → IRE1 ↑→ XBP1 ↑→ FOXO1 ↓	[64]
PERK ↑→ FOXO1 ↑	[65]
ER stress ↑→... → ATF4 ↑→ CHOP ↑→ TRB3 ↑→ AKT ↓	[40, 41]
IL-6 ↑→ JAK ↑→ STAT3 ↑→ SOCS3 ↑→ IRS ↓	[66–68]