The genes encoding hepatocyte nuclear factor 3 (HNF3) proteins play a pivotal role in the regulation of metabolism and in the differentiation of metabolic tissues such as the pancreas and liver. HNF3 transcription factors bind to cis-regulatory elements in hundreds of genes encoding gluconeogenic and glycolytic enzymes, serum proteins and hormones. Genetic analysis in mice has shown that HNF3 beta is necessary for the development of the foregut endoderm, from which the liver and pancreas arise. HNF3 alpha is required for the full activation of glucagon in the pancreas, whereas HNF3 gamma induces the activation of gluconeogenic enzymes to prevent hypoglycemia during fasting.