Impairments in insulin signalling including decreased IRS1 protein content, reduced Akt Ser473 phosphorylation, impaired insulin-stimulated PI3K activity and impaired glucose transport have been observed in adipocytes from individuals with a predisposition toward type 2 diabetes (i.e. with at least two first-degree relatives diagnosed with diabetes) [28]. This evidence concerns the gene IRS1 and diabetes mellitus.