Dipeptidyl peptidase IV inhibitors in diabetes: more than inhibition of glucagon-like peptide-1 metabolism?
Inhibitors of the protease dipeptidyl peptidase IV (DPP-IV) are promising new drugs for the treatment of type 2 diabetes. They are thought to act by inhibiting the breakdown of glucagon-like peptide-1 and, thereby, selectively enhancing insulin release under conditions when it is physiologically required. These drugs are selective for DPP-IV, but the enzyme itself has a broad range of substrates other than glucagon-like peptide-1. Other high affinity substrates of DPP-IV including peptide YY may also play a role in the regulation of energy homeostasis. Moreover, DPP-IV is also known as CD26 and considered to be a moonlighting protein because it has a wide range of other functions unrelated to energy homeostasis, e.g. in immunity. The potential role of DPP-IV inhibition on substrates other than glucagon-like peptide-1 in diabetes patients remains to be elucidated.
Michel
Martin C
MC
Fliers
Eric
E
Van Noorden
Cornelis J F
CJ
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D016503:Drug Delivery Systems; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4