Accounting for near-normal glucose sensitivity in K_ir6.2[AAA] transgenic mice

K_ir6.2[AAA] transgenic mouse islets exhibit mosaicism such that ∼70% of the β-cells have nonfunctional ATP-sensitive potassium (K _ATP) channels, whereas the remainder have normal K_ATP function. Despite this drastic reduction, the glucose dose-response curve is only shifted by ∼2 mM. We use a previously published mathematical model, in which K_ATP conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of K_ATP conductance. Compensation is favored by the assumption that only a small fraction of K_ATP channels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of calcium. We show further that strong gap-junctional coupling of both membrane potential and calcium is needed to overcome the stark heterogeneity of cell properties in these mosaic islets.