Acute Insulin Response Studies

Acute Insulin Response Studies

Many, but not all patients with KATP HI show a characteristic acute insulin response to an injection of Ca²⁺, since the voltage-gated Ca²⁺ channels in the membrane of affected ß-cells are open most of the time (23). In theory, acute insulin response studies should also be able to differentiate between diffuse and focal KATP HI: In patients with diffuse KATP HI, administration of tolbutamide (a sulfonylurea compound that binds to the ABCC8-encoded subunit of KATP channels, causing the channels to close and insulin to be released) should not lead to an acute insulin response, since the KATP channels in ß-cell membranes are defective and should thus no longer be sensitive to tolbutamide action. In focal KATP HI, the remaining intact KATP channels outside of the focal lesions should give rise to an acute insulin response to tolbutamide. Contrary to these expectations, however, KATP channels affected by KATP HI-associated mutations show residual sensitivity to tolbutamide action, so that the focal and diffuse forms of KATP HI often cannot be distinguished by acute insulin response studies (15, 24).