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) Y 1 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 Y 1 receptor activation [36] |
|
| |
| Liver | Improve hepatic steatosis [37] |
|
| |
| Neuro-endocrine systems | (i) Increase plasma norepinephrine after meals [38] (ii) Enhance Y 1 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.