ObjectiveTo explore the action of dominant-negative effect on mutant insulin gene-induced diabetes.Methods293T cells were transfected with a recombinant plasmid containing mutant preproinsulinogen complementary DNA (cDNA) and a recombinant plasmid containing human wild-type preproinsulinogen cDNA. There were 5 mutant groups which mutant preproinsulins respectively bear substitutions V(A3)L, C(A7)Y, R(SP6)H, G(B8)S or G(C28)R. Wild-type mouse preproinsulin and wild-type human preproinsulin were co-transfected as normal control group. After 48 hours, medium and cells were collected. Human proinsulin were detected by human-specific proinsulin radioimmunoassay.ResultsCompared with the control group [(135.84±1.89) pmol/L], human proinsulin levels in medium of C(A7)Y group [(29.28±6.85) pmol/L] and G(B8)S group[(33.62±10.52) pmol/L] decreased significantly (P<0.01). There was no significant difference in human proinsulin level between the other groups and the control group (P>0.05).ConclusionMutants C(A7)Y and G(B8)S induce the dominant-negative effect on co-existing wild-type proinsulin.