The effects of 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB), an inhibitor of the volume-sensitive anion channel (VSAC), on the function of pancreatic β-cells were investigated. Rats were killed humanely and islets isolated by collagenase digestion. Islets were then dispersed into single cells by brief exposure to a Ca²⁺-free buffer. Insulin-secreting β-cells were identified by size and response to glucose. The whole-cell, cell-attached and perforated patch configurations of the patch-clamp technique were used to study ion channel and electrical activity. Insulin release was measured by radioimmunoassay from intact islets.

In 6/6 cells, DCPIB inhibited VSAC activity under conventional whole-cell conditions with IC₅₀ values of 2.2 and 1.7 mM for inhibition of outward and inward currents, respectively. DCPIB also suppressed glucose-induced electrical activity in 5/5 β-cells over the concentration range 0.1-10 mM. With lower concentrations of the drug, this inhibitory effect occurred after a longer delay. DCPIB hyperpolarised the cell membrane potential at a sub-stimulatory glucose concentration in 3/3 cells. The suppression of electrical activity by DCPIB was associated with a marked inhibition of glucose-stimulated insulin release from intact islets (P < 0.01 at 1 µM DCPIB). K_ATP channel activity in cell-attached patches was unaffected by DCPIB, whilst the drug produced a modest, non-significant reduction in whole-cell input conductance, presumably reflecting VSAC inhibition.

It is concluded that DCPIB inhibits electrical and secretory activity in the β-cell as a result of VSAC inhibition and hyperpolarisation of the β-cell membrane potential. This finding strongly supports our earlier suggestion that glucose stimulates β-cell function, at least in part, by activating the VSAC.

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