ABSTRACT

This chapter discusses the findings of molecular genetic studies that have helped to clarify aspects of the tissue-specific structure and regulation of glucokinase. The tissue-specific expression of an active glucokinase molecule is achieved by regulation occurring at several steps in the transcription and processing of the glucokinase mRNA. In order to understand the mechanisms underlying the tissue-specific regulation of glucokinase, the cloning of a cDNA for the enzyme was required. The various characteristics of glucokinase suggest that the enzyme is more similar to yeast hexokinase than it is to the mammalian hexokinase types I through III. By recognizing and modulating the rate of glucose phosphorylation, glucokinase acts as the rate-limiting determinant for glucose usage by the ß cell. In liver, glucokinase is regulated differently than in the islet, thus reflecting the different physiologic role of the enzyme in the hepatocyte. The cloning of hepatic glucokinase permitted studies of islet glucokinase gene expression to be initiated.