Out data therefore indicate that a new dimension to the physiology and pathophysiology of insulin sensitivity and insulin resistance involves changes in the degree of lysine acetylation of IRS-1 and that specific small molecule inhibitors of HDAC2 activity could represent novel therapeutics for the treatment of diseases that centre around insulin resistance, such as type 2 diabetes and obesity. The gene discussed is HDAC2; the disease is obesity due to melanocortin 4 receptor deficiency.