title: Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP-1R in renal tubular epithelial cells.
abstract: Tubular atrophy and dysfunction is a critical process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney failure associated with glucotoxicity. Autophagy is a cellular pathway involved in protein and organelle degradation. It is associated with many types of cellular homeostasis and human diseases. To date, little is known of the association between high concentrations of glucose and autophagy in renal tubular cells. In the present study, we investigated high glucose-induced toxicity in renal tubular epithelial cells by means of several complementary assays, including cell viability, cell death assays and changes in ultrastructure in an immortalized human kidney cell line, HK-2 cells. The extent of apoptosis was significantly increased in the HK-2 cells following treatment with high levels of glucose. In addition, in in vivo experiments using diabetic rats, high glucose exerted harmful effects on the tissue structure of the kidneys in the diabetic rats. Chronic exposure of the HK-2 cells and tubular epithelial cells of nephritic rats to high levels of glucose induced autophagy. Liraglutide inhibited these effects; however, treatment witht a glucagon-like peptide-1 receptor (GLP‑1R) antagonist enhanced these effects. Our results also indicated that the exposure of the renal tubular epithelial cells to high glucose concentrations in vitro led to the downregulation of GLP-1R expression. Liraglutide reversed this effect, while the GLP-1R antagonist promoted it, promoting autophagy, suggesting that liraglutide exerts a renoprotective effect in the presence of high glucose, at least in part, by inhibiting autophagy and increasing GLP-1R expression in the HK-2 cells and kidneys of diabetic rats.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: G
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of The Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology*; D000069450:Liraglutide; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism*
chemical_list: D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D008869:Microtubule-Associated Proteins; D018027:Receptors, Glucagon; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; C526109:Anxa3 protein, rat