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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) [2830]
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 [3133]
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 [5557]
(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 [5961]
GSK3 β→ GS → glycogen synthesis [42, 43]
FOXO1 → PEPCK , G6PC → glucose synthesis [47, 4749]
(mTORC1 + S6K) → IRS [4446]
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 [6668]