PIK3R1 and Insulin resistance: Conversely, previously described patients with a loss-of-function mutation in AKT2 had insulin resistance, with severe fatty liver and dyslipidemia, quite unlike patients with severe insulin resistance due either to mutations in the insulin receptor (9), who exhibit normal hepatic lipid content, normal rates of fasting de novo lipogenesis, and a normal plasma lipid profile despite severe insulin resistance, or to mutations in PIK3R1, encoding a regulatory subunit of PI3K, who also show a normal lipid profile despite severe insulin resistance (16).