Edwin Bernard Villhauer

Chapter 19. DPP-IV inhibition and therapeutic potential

Publisher Summary This chapter elaborates the dipeptidyl peptidase IV (DPP-IV) inhibition and therapeutic potential. DPP-IVs structural characteristics, proteolytic substrate requirements, and the profile of key and new inhibitors of its catalytic function are presented. With a half-life of more than 96 hours, DPP-IV is constitutively expressed by a variety of cell types, particularly on differentiated epithelial cells of the intestine, liver, prostate tissue, corpus luteum, and kidney proximal tubules as well as leukocyte subsets, such as T-helper lymphocytes and subsets of macrophages. The DPP-IV gene and its associated cDNAs from human, mouse, and rat tissue have been cloned. A single gene encoding DPP-IV has been localized to human chromosome 2 and encodes two mRNA species sized at approximately 2.8 and 4.2 kb that are present in most tissues producing DPP-IV. GLP-1 stimulates glucose-dependent insulin secretion, inhibits glucagon release, slows gastric emptying, promotes growth and differentiation of p-cells, and stimulates insulin gene expression and biosynthesis. The in vitro and in vivo studies in mice, rats, and humans have shown that DPP-IV is the primary inactivation pathway for the intestinal growth factor, GLP-2.