VBIT-4

VBIT-4 rapidly inhibits the loss of ATP, which is a consequence of its translocation to the plasma membrane caused by VDAC1 overexpression, in plVdac1-expressing INS-1 cells.^[2]

Effect of VDAC1 antibody (VDAC1-ab, 10 nM), metformin, or the VDAC1 inhibitors AKOS022075291 and VBIT-4 (20 μM each) on ATP release after 1 hr exposure at 1 mM glucose of INS-1 cells transfected with control plasmid or plVdac1. ATP content and release from isolated mouse or human islets or from INS-1 cells after transfection with mitochondrial targeted VDAC1 (mtVDAC1) or plasma membrane targeted VDAC1 (plVDAC1) plasmids was determined using a luminometric assay kit. After incubation of islets (50/vial) or INS-1 cells for 60 min, an aliquot of the media was removed for subsequent measurements of released ATP. Then the islets or INS-1 cells were washed 3 times and the lysates were used for measurements of ATP and protein contents.

VBIT-4 prevents increases in water consumption and polyuria in the db/db mice, also counteracts VDAC1 overexpression, preventing mistargeting to the β cell surface under glucotoxic conditions. Through the prevention of VDAC1 gene expression, VBIT-4 may have disease-modifying actions.^[2]