Figure 2.

Impact of VDAC1 on β Cell Function

(A and B) Glucose-stimulated insulin secretion (GSIS) in INS-1 cells after overexpression of Vdac1 (OE) (A) or knockdown (KD) of Vdac2 (B) (n = 5).

(C) Oxygen consumption rate (OCR) in INS-1 cells after overexpression of Vdac1 or KD of Vdac2. Subsequent additions were as follows: oligomycin ([Olig], an inhibitor of ATP synthase) (0.4 μM), dinitrophenol ([DNP], an uncoupler) (0.4 μM), and rotenone ([Rot], an inhibitor of complex (I) (0.1 μM).

(D) Area under the curve (AUC) for the experiments in (C) (n = 5).

(E and F) OCR of INS-1 cells cultured at 5 or 20 mM glucose (72 hr) (n = 5).

(G) VDAC1 silencing protects human islet cells from glucotoxicity-induced decrease in cellular reductive capacity (formazone production), while VDAC2 KD is harmful. Islets from five donors (used in separate experiments) were cultured at either 5 or 20 mM glucose for 72 hr.

(H) Effect of VDAC1 or VDAC2 KD on ATP content of islets cultured at 5 or 20 mM glucose (72 hr) and incubated at 1 or 16.7 mM glucose for 1 hr (n = 3 donors).

(I) Insulin secretion for the same islets as in (H).