The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors
Table 1
The important functions of DASH molecules.
Molecules
Functions
Soluble form in the blood
DPP-4
Type II membrane glycoprotein with dipeptidyl peptidase activity
Yes
FAP (Seprase)
(i) Type II membrane glycoprotein with dipeptidyl peptidase, collagenase, and gelatinase activity (ii) Involved in extracellular matrix degradation, tissue remodeling, and fibrosis [15] (iii) Can heterodimerize with DPP-4 for efficient tissue remodeling [16]
Yes
DPP-7 (QPP, DPP-II)
(i) Intracellular location with dipeptidyl peptidase activity (ii) Most of its physiological substrate is unknown (iii) Secreted in an active form in response to calcium [17] (iv) Regulation of apoptotic pathway in quiescent lymphocytes [17]
Unknown
DPP-8/DPP-9
(i) Intracellular localization with dipeptidyl peptidase activity (ii) Seems to be involved in M1 macrophage activation [18] (iii) Up-regulation of DPP-9 during monocyte to macrophage differentiation [18] (iv) Can cleave releasable neuropeptide Y (NPY) in brain [19] (v) The regulation of cellular proliferation and apoptosis [19]
No
DPP-6 and DPP-10
(i) Transmembrane proteins with no peptidase activity (ii) Binds to specific voltage-gated K+ channels, altering their structures and biophysical properties [20]