It is possible that the association of this locus with T2DM may be driven by more than one mechanism (29), i.e., that overactive TALK-1 and overexpression of TALK-2 may both contribute to hyperpolarization of the β cell Vm, reducing glucose-stimulated Ca2+ influx and GSIS. This evidence concerns the gene KCNK16 and type 2 diabetes mellitus.