The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors

Table 3

Various non-glycemic actions of DPP-4 inhibitors.

Tissues/systems	Effects of DPP-4 inhibitor
Heart	(i) Reduce infarct size after myocardial ischemia/reperfusion injury [21]; (ii) Decrease cardiac fibrosis in uremic cardiomyopathy model [22]; (iii) Prevent left ventricular hypertrophy caused by continuous infusion of isoproterenol [23]
Vascular systems	(i) Decrease RAGE expression [24]; (ii) Vascular relaxation and increase nitric oxide release [25]; (iii) Reduce atherosclerotic lesion [26]; (iv) Attenuate soluble DPP-4-induced VSMC proliferation [27]; (v) Increase the number of circulating EPCs and plasma level of SDF-1𝛼 in type 2 diabetic patients [28]; (vi) Neuroprotective in ischemic stroke model [29]; (vii) Reduce lipid and protein oxidation [30]; (viii) Abolish the BP-lowering effects of enalapril in patients with metabolic syndrome [31]; (ix) Prothrombotic effect [32]; (x) 𝑌1 receptor-mediated endothelial and medial hypertrophy/hyperplasia of arterioles in a specific condition [33]
Kidney	(i) Decrease NaHCO3 reabsorption in renal proximal tubule by inhibiting Na^+/H^+ exchanger type 3 activity [34]; (ii) Inhibit glomerulosclerosis, fibrosis, and albuminuria [35]; (iii) Stimulate extracellular matrix production in mesangial cells mediated by 𝑌1 receptor activation [36]
Liver	Improve hepatic steatosis [37]
Neuro-endocrine systems	(i) Increase plasma norepinephrine after meals [38]; (ii) Enhance 𝑌1 receptor-mediated renovascular responses to Angiotensin II in kidneys from genetically-susceptible kidneys [39]
Immune systems	(i) Suppress MMP-1, proliferation and some cytokine production (IL-6, IL-1𝛽) in histiocytic cell lines [40, 41]; (ii) Anti-inflammatory actions [42]; (iii) Attenuation of ischemia/reperfusion injury in lung transplants in association with increased levels of intrapulmonary VIP [43]; (iv) May inhibit the cytopathic effects of HIV-1 [8]
Hematopoietic system	(i) Anti-platelet effect [44]; (ii) Increased recovery of hematopoiesis after bone marrow suppression; (iii) Expansion of HPCs [45, 46]

Note: presumed problematic actions that may cause adverse CV effects are in italic.