Glucokinase is expressed in both the liver and the pancreatic p-cell and plays a key role in the metabolism of glucose by both tissues. Expression of this enzyme is differentially regulated; hepatic glucokinase is stimulated by insulin and repressed by CAMP, whereas p-cell glucokinase activity is increased by glucose. Recently, the glucokinase gene has been characterized and was found to contain two different transcription control regions. One region regulates transcription of the gene in the liver, whereas the other region, which lies at least 12 kilobases further upstream, controls transcription in the pancreatic p-cell. The finding of two different transcription control regions in a single glucokinase gene provides a genetic basis for the tissue-specific differential