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The discovery about insulin that exhibits binding affinity toward G-quadruplex DNA oligonucleotide formed by a two-repeat length of the insulin-linked polymorphic region (ILPR) consensus sequence is reported. The discovery raises the possibility that insulin might bind to G-quadruplex DNA formed in the insulin-linked polymorphic region in vivo and thereby plays a role in modulation of insulin gene expression, and it provides a basis for design of insulin analogues to probe this hypothesis.