Therapeutic potential of dipeptidyl peptidase IV inhibitors for the treatment of type 2 diabetes.
Incretins are peptide hormones, exemplified by glucose-dependent insulinotropic peptide and glucagon-like peptide 1 that are released from the gut in response to nutrient ingestion and enhance glucose-stimulated insulin secretion. Incretin action is terminated due to N-terminal cleavage of the peptides by the aminopeptidase dipeptidyl peptidase IV (DPP-IV). Hence, inhibition of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 degradation via reduction of DPP-IV activity represents an innovative strategy for enhancing incretin action in vivo. This review summarises the biology of incretin action, the structure, expression and pleiotropic biological activities of DPP-IV and provides an overview of the rationale, potential merits and theoretical pitfalls in the development of DPP-IV inhibitors for the treatment of type 2 diabetes.
Drucker
Daniel J
DJ
Department of Medicine, Banting and Best Diabetes Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, M5G 2C4, Canada. d.drucker@utoronto.ca
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D015842:Serine Proteinase Inhibitors; D018819:Dipeptidyl Peptidase 4