Substrates that may have clinical relevance | GLP-1, GIP,a GLP-2,b neuropeptide Y,c peptide YY, PACAP, substance P, RANTES, and other chemokines such as stromal cell-derived factor, eotaxin, and macrophage-derived chemokines, which may modulate immune function. |
Substrates with questionable clinical relevance | GRP, GRH, IGF-1, prolactin, HCG, bradykinin, Interleukin-1β, interleukin-2, trypsinogen (Heymann et al., 1986; Erlanson-Albertsson and Larsson, 1988) procolipase (which affects enterostatin, by which the lipid uptake is regulated) (Bouras et al., 1996). |
PACAP, pituitary adenylate cyclase-activating polypeptide; RANTES, regulated on activation normal T cells expressed and secreted; GRP, gastrin-releasing peptide; GRH, growth hormone-releasing hormone/somatoliberin; IGF, insulin-like growth factor; HCG, human chorionic gonadotropin.
↵a The DPP-4 inhibition is accompanied by a rise in both the relevant incretins, GLP-1 and GIP, which should have been anticipated to have more effect than administering only a GLP-1 analog/mimetic.
↵b No antidiabetic effect (only intestinal, parathormone, bone, and gut motility effects) (Mentlein et al., 1993).
↵c One of the most orexigenic peptides (Bray, 1993; Chance and Fischer, 1993; Karydis and Tolis, 1998). The inhibition of neuropeptide Y degradation has an impact on its orexigenic effect (Karl et al., 2003b), on effect on GI motility (Chen et al., 1997), on behavior and probably stress-induced analgesia (Karl et al., 2003a), and stimulation of food intake and feeding motivation.