Dipeptidyl peptidase IV (DPP-IV) inhibition

Dipeptidyl peptidase IV (DPP-IV) also known as “Gly-Pro naphthylamidase” is the unique cell membrane protease cleaving X-Pro dipeptides from the N-terminal end of peptides and proteins. It plays an important role in glucose homeostasis through proteolytic inactivation of incretin hormones, primarily glucagon like peptide-1 (GLP-1) which is critical in sugar balance.

GLP-1 has a short lifetime due to rapid degradation by the DPP-IV enzyme, which cleaves the two N-terminal amino acids to give the inactive GLP-1 amide. Thus, inhibition of DPP-IV, which leads to increases in the circulating level of GLP-1, is an important approach for the treatment of type 2 diabetes.

GLy-Pro-AMC (substrate) when added to plasma gives a linear and proportional reaction mediated by Dipeptidyl peptidase enzyme resulting in two products namely 7 AminoMethyl coumarin and GLy-Pro. The formation of these products are to be estimated as a measure of DPPIV activity and in a clinical corresponds to plasma derived from subjects prior to treatment. In the presence of a DPPIV inhibiors in plasma (e.g. Vildagliptine, Teneligliptin, sitagliptin), as would happen with drug treated subject samples, the formation of the above products are reduced. This reduction when compared to samples which does not contain these inhibitors (as is the case of plasma from subjects before treatment) can be expressed as percentage inhibition of DPPIV activity due to drug treatment at every sampling time point. Thus one can assess the Percentage inhibition of DPPIV activity at each sampling time point.