The pancreatic β-cell recognition of insulin secretagogues. VII. Binding and permeation of chloromercuribenzene-p-sulphonic acid in the plasma membrane of pancreatic β-cells

The uptake of chloromercuribenzene-p-sulphonic acid (CMBS) was studied in microdissected pancreatic islets of ob/ob-mice. After rapid initial binding, the uptake increased linearly with time, suggesting that CMBS diffused into the plasma membrane. The binding of CMBS was rapidly reversed on exposure to l-cysteine. Whereas glibenclamide had no effect, glucose and 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonic acid (SITS) inhibited diffusion without affecting the initial binding. SITS, but not glucose, also inhibited CMBS-induced insulin release. The results support the hypothesis that CMBS stimulates insulin release by reacting with thiol groups in the β-cell plasma membrane. These thiol groups may be located in an anion diffusion channel, entrance to which is blocked by SITS and exit from which is inhibited by glucose. In comparison with erythrocytes, the β-cells contain a large number of superficial thiol groups, which may explain why these cells accumulate alloxan.