Sitagliptin ameliorates ER stress in diabetic kidney disease through upregulation of SIRT1

Abstract Objectives Endoplasmic reticulum (ER) stress plays a significant role in the progression of diabetic kidney disease (DKD), and dipeptidyl peptidase-4 (DPP4) inhibitors are widely used antihyperglycemic agents, exerting renal beneficial effects DKD. Here, we investigated DPP4 inhibitor Sitagliptin (Sita) ER homeostasis kidneys DBA2/J (D2) mice albumin-stimulated HK-2 cells. Methods Results was observed both vivo vitro , as reflected by notably increased glucose-regulated protein 78 kDa (GRP78), CHOP, high phosphorylation PERK (p-PERK), cleaved caspase3 (c-CASP3), whereas Sita effectively attenuated these disorders. Meanwhile, expression SIRT1 . To further validate potential regulating stress, regulated siRNA overexpressed plasmids albumin-overloaded Elevated alleviated albumin-induced while decreased aggravated albumin-treated Conclusion The results suggest that novel mechanism links enzyme to during tubular injury DKD highlight may be target for managing