Aim: Diabetic nephropathy (DN) is a type of microvascular complication that arises from diabetes mellitus and leads to further health issues. Most importantly, the prevalence of DN is steadily rising in developed countries. This research explored the therapeutic benefits of alogliptin, a dipeptidyl peptidase IV (DPP-4) inhibitor, on streptozotocin (STZ)-induced DN and its underlying mechanisms in rats.
Main methods: Ten rats were allocated to group 1, served as the normal group; and received saline. To develop diabetes, thirty rats were administered a single intraperitoneal dose of STZ (45 mg/kg). STZ-induced diabetic rats were randomly assigned to three groups: group 2 diabetic control; was given saline, groups 3 and 4 received alogliptin (10 mg/kg) and (20 mg/kg), respectively. The treatment began 8 weeks after diabetes onset and continued for four weeks. Histopathological alterations in the kidney were detected. Serum was collected to measure blood glucose levels (BGL), renal function, and lactate dehydrogenase (LDH). Tissue samples were collected to detect changes in oxidative stress (OS), inflammation, 5' adenosine monophosphate-activated protein kinase (AMPK), and the mammalian target of Rapamycin (mTOR) signaling pathways in addition to apoptotic and autophagy changes.
Key findings: Alogliptin reduced STZ-induced histological changes in the kidney as well as OS, and inflammation. Alogliptin also ameliorated the AMPK/mTOR signaling pathways, enhanced autophagy, and reduced apoptosis.
Significance: These results demonstrate that alogliptin ameliorates inflammation and OS and consequently modulates the AMPK/mTOR axis along with targeting autophagy and apoptosis, leading to the alleviation of DN.
Keywords: AMPK; Alogliptin; Apoptosis; Autophagy; DKD; mTOR.
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