Analysis of amino acid sequences of insulinotropic polypeptides revealed a common short fragment consisting of four amino acid residues. We synthesized KEDW_a tetrapeptide, analog of this fragment protected from the effects of gastrointestinal proteinases. This tetrapeptide partially restored insulin synthesis in rats with alloxan-induced diabetes. The slope of the sugar curve in this case was similar to that in normal animals. Presumably, this tetrapeptide activates the preproinsulin gene promotor site via complementary interactions with the ggcagg and cctgcc nucleotide sequences of the leading strand of double-stranded DNA.