Instead, α-cell-activation may have a prerequisite role in β-cell-activation: (i) without the MT1 involved, melatonin treatment would not show significant effects on insulin release [30]; and (ii) a number of single nucleotide polymorphisms in the MTNR1B gene that encode for MT2 are involved in the pathogenesis of T2D [32], however, loss-of-function mutations in or removal of MT1 would significantly impair the ability to metabolize glucose [33]. This evidence concerns the gene MTNR1B and type 2 diabetes mellitus.