Insulin Gene Expression

Publisher Summary This chapter focuses on the molecular mechanisms controlling expression of the insulin gene, and the regulation of proinsulin biosynthesis. Insulin is a small globular protein (5.8 kDa) consisting of two peptide chains, designated A and B, linked together by disulphide bridges. Insulin is synthesized in the β-cell s of the islets of Langerhans as a larger precursor molecule, preproinsulin, which undergoes post-translational processing during its transit through the secretory pathway. Preproinsulin contains an NH 2 -terminal 24-amino acid hydrophobic signal peptide. The signal peptide is removed in the endoplasmic reticulum to generate proinsulin, in which the insulin B chain and A chain are linked by a connecting peptide, C-peptide. Insulin is a member of a superfamily of structurally related peptides, which includes the ovarian hormone relaxin, and insulin-like growth factors I and II (IGF-I and IGF-II). The insulin gene is simple with the major regulatory elements that determine when and where the gene is expressed located in a small region adjacent to the start site. Within this region, most of the transcriptionally active elements have been mapped and proteins capable of binding at these sites, some of which exhibit transcriptional activity, identified. Despite this progress, a model describing the molecular mechanisms whereby the insulin gene is regulated has not been formulated.