Although GLP-1 is the primary DPP-4 substrate, DPP-4 also cleaves multiple peptides including GIP, stromal cell derived factor type 1 α (SDF1α), neuropeptide Y (NPY), peptide YY (PYY), B-type (brain) natriuretic peptide (BNP), glucagon like peptide-2, and other substrates [ 47].
Although GLP-1 is viewed as an important DPP-4 substrate able to influence cardiovascular function, DPP-4 cleaves multiple peptides, which may have direct actions on the heart and blood vessels (20).
Interestingly, stromal cell-derived factor (SDF -1α iSDF -1αural DPP-4 substrate and a major regulator of stem cell mobisizationatural, as well as EPCs/PACs function [ 14].
These results suggested the possibility that DPP-IV inhibitor may stimulate insulin biosynthesis via the intracellular cAMP accumulation by incretins and presumably unknown DPP-IV substrate(s).
Among the DPP-4 substrate chemokines, stromal cell-derived factor-1 (SDF-1) has been intensively studied.
Further elucidation of DPP-4 substrates is required.
And, there is a plethora of DPP-4 substrates and DPP-4-interacting molecules.
However, studies about DPP-4 substrates other than GIP and GLP-1 are limited.
In addition, DPP-4 substrates are proline- and alanine-containing peptides, including various growth factors, chemokines, neuropeptides and vasoactive peptides.
In the present study, we could not measure other DPP-4 substrates, such as BNP [ 24], because of sample limitation.
