Inhibition of dipeptidylpeptidase IV activity as a therapy of type 2 diabetes.
Dipeptidyl peptidase IV (DPP IV) is a ubiquitous, multifunctional, serine protease enzyme and receptor with roles in the control of endocrine and immune function, cell metabolism, growth and adhesion. As an enzyme, DPP IV cleaves the N-terminal dipeptide from the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. This inactivates the hormones, thereby cancelling their prandial insulinotropic effect. One approach to restore incretin activity as a therapy for Type 2 diabetes has been the development of DPP IV inhibitors. Inhibitors of DPP IV have shown efficacy and tolerability when used to control the hyperglycaemia of noninsulin-dependent animal models and human Type 2 diabetes. These DPP IV inhibitors prolong active incretin hormone concentrations and may exert additional antidiabetic effects. If long-term clinical trials confirm sustained and safe control of blood glucose, DPP IV inhibitors (known as 'gliptins') may be expected to provide a new treatment modality for Type 2 diabetes.
Green
Brian D
BD
Queens University Belfast, School of Biological Sciences, David Keir Building, Stranmillis Road, Belfast BT9 5AG, Northern Ireland. b.green@ulster.ac.uk
Flatt
Peter R
PR
Bailey
Clifford J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4