IRS1 and type 2 diabetes mellitus: Moreover, IRS1 and IRS2 show differential relevance in mitogenic and metabolic insulin effects, respectively, as IRS1-KO mice are 50% smaller in size and insulin resistant but maintain normal glucose tolerance due to compensatory β-cell hyperplasia [3], whereas IRS2-KO mice develop type 2 diabetes due to β-cell failure [4] and decreased suppression of endogenous glucose production and hepatic glycogen synthesis [2].