Abstract

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus that commonly leads to end-stage renal disease. The pathophysiology of diabetic-induced nephropathy is complex, and its precise mechanism is not fully understood. When the hormones of the incretins group become dysregulated, namely, glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), they contribute to DN development. Dipeptidyl peptidase-4 (DPP-4) deactivates GIP and GLP-1, and therefore DPP-4 inhibitors have a positive impact on microvascular complications and improve the outcomes of DN (Avogaro et al., 2014). Protein tyrosine phosphatase 1B (PTP1B) plays a critical role in controlling glucose uptake and regulating insulin. It can also be considered a negative regulator of the JAK-STAT signaling pathway, one that results in the alleviation of inflammation (Marrero et al., 2006). Therefore, there is a key link between PTP1B and inflammation, which plays a major role in DN development. Unfortunately, current data on the relationship between DPP-4 inhibition and the PTP1B/JAK-STAT pathway and its effect on DN is insufficient to drawing robust conclusions, however, there is data suggesting that sitagliptin, a DPP-4 inhibitor, can mitigate oxidative stress and inflammation (Wang et al., 2018), which plays a major role in DN pathogenesis.