Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

摘要: Since relative or absolute insulin deficiency and insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability coding region receptor substrate-1 (IRS-1), a candidate gene that is ubiquitous insulin-sensitive insulin-like growth factor 1 (IGF1) sensitive tissues, including those determine glucose production clearance regulatory effects on pancreatic beta-cell function. IRS-1 has central role as an adaptor molecule links insulin-receptor IGF1-receptor kinases enzymes regulate cellular metabolism growth. Single-stranded conformation polymorphism analysis direct nucleotide sequencing were applied to genomic DNA from 86 unrelated 76 normoglycaemic controls. 10 3 controls heterozygous at codon 972 for which glycine was substituted arginine. Moreover, 513, 6 2 had transition alanine proline. None carriers both aminoacid variants total allelic frequency polymorphisms about three times higher than (p = 0.02). Both substitutions located close tyrosine phosphorylation motifs putative recognition sites IGF1 signal transmission proteins. Analysis phenotypes showed who did not differ their degree resistance compared without known polymorphisms. However, variant significantly lower plasma levels fasting C-peptide. Our results suggest may be subset late-onset NIDDM.