Targeting Sur1/Abcc8-Type Neuroendocrine K-Atp Channels In Pancreatic Islet Cells

ATP-sensitive K+ (K-ATP) channels play a regulatory role in hormone-secreting pancreatic islet alpha-, beta- and delta-cells. Targeted channel deletion would assist analysis and dissection of the intraislet regulatory network. Toward this end Abcc8/Sur1 flox mice were generated and tested by crossing with glucagon-(GCG)-cre mice to target alpha-cell K-ATP channels selectively. Agonist resistance was used to quantify the percent of alpha-cells lacking channels. 41% of Sur1(loxP/loxP);GCG-cre(+) and similar to 64% of Sur1(loxP/-);GCG-cre(+) alpha-cells lacked K-ATP channels, while similar to 65% of alpha-cells expressed enhanced yellow fluorescent protein (EYFP) in ROSA-EYFP/GCG-cre matings. The results are consistent with a stochastic two-recombination event mechanism and a requirement that both floxed alleles are deleted.