Naturally-occurring single-nucleotide polymorphisms of α2 -AR overexpression decrease insulin secretion (both first phase GSIS and basal) and increase the risk of type 2 diabetes mellitus (T2DM) in human and rat, via impaired granule docking at the plasma membrane and beta cell exocytosis, at stage distal to elevation of (Ca2+)i [73]. This evidence concerns the gene INS and type 2 diabetes mellitus.