Transcriptional Program Causing VDAC1 Overexpression after Glucotoxicity
(A) ChREBP and TXNIP mRNA is increased in T2D islets (n = 4–5 donors).
(B) Vdac1 overexpression is blunted after silencing of either Chrebp or Txnip in 20 mM glucose-cultured INS-1 cells (n = 5).
(C) Glucose-evoked ChREBP induction is prevented in histone acetyltransferase p300 knockout INS-1 (Ep300−/−) cells.
(D) Txnip expression is suppressed in INS-1 (Ep300−/−) cells after 5 mM glucose culture. Txnip induction is blunted at 20 mM glucose.
(E) VDAC1 is not induced by glucotoxicity in INS-1 (Ep300−/−) cells.
(F) VDAC2 is upregulated in INS-1 (Ep300−/−) cells at 5 mM and further increased after culture at 20 mM glucose (n = 3–4).
(G) INS-1 (Ep300−/−) cells are partially protected from blunting of GSIS after culture at 20 mM glucose (n = 3–4). Independent experiments given as n.