title: Gemigliptin improves renal function and attenuates podocyte injury in mice with diabetic nephropathy.
abstract: Podocytes participate in the formation and regulation of the glomerular filtration barrier. Loss of podocytes occurs during the early stages of diabetic nephropathy and impairs glomerular filtration. Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as anti-diabetic agents in clinical practice. In this study, we showed that gemigliptin, a novel DPP-4 inhibitor, reduced podocyte apoptosis in type 2 diabetic db/db mice without reducing hyperglycemia. Gemigliptin (100mg/kg/day) was administered orally for 12 weeks in db/db mice. Blood glucose levels and albuminuria were measured. The renal cortex was collected for histological examination, and molecular assays were used to detect 8-hydroxydeoxyguanosine, advanced oxidation protein products (AOPP), the receptor for advanced glycation end products (RAGE), and integrin-linked kinase (ILK). Type 2 diabetic db/db mice exhibited albuminuria, renal histopathological changes, and podocyte loss. Administration of gemigliptin to db/db mice suppressed albuminuria, enzyme activity and expression of DPP-4, and podocyte apoptosis. The effect of gemigliptin on diabetes-induced podocyte loss was associated with the suppression of oxidative damage, AOPP accumulation, RAGE expression, and ILK expression. These results indicate the possible benefits of using gemigliptin in diabetes patients to treat renal impairment without affecting glycemic control.
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; LG Life Sciences Ltd., R&D Park, Daejeon 305-343, South Korea.
authors.forename: Eunsoo
authors.initials: E
authors.lastname: Jung
authors.affiliation: Korean Medicine Based Herbal Drug Development Group, Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: LG Life Sciences Ltd., R&D Park, Daejeon 305-343, South Korea.
authors.forename: Sung
authors.initials: S
authors.lastname: Ho Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Sanghwa
authors.initials: S
authors.lastname: Kim
authors.affiliation: Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, South Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, South Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 443-270, South Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D062107:Advanced Oxidation Protein Products / Q000378:metabolism; D000419:Albuminuria / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010881:Piperidones / Q000494:pharmacology*; D050199:Podocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D062107:Advanced Oxidation Protein Products; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006147:Guanine; D010881:Piperidones; D017346:Protein Serine-Threonine Kinases; D011743:Pyrimidines; D000067759:Receptor for Advanced Glycation End Products; D000099200:Scaffold Protein ILK; C000593873:Ager protein, mouse; C534891:LC15-0444; C078307:8-oxo-7,8-dihydrodeoxyguanine; C545245:Dpp4 protein, mouse
keywords: Apoptosis; Diabetic nephropathy; Gemigliptin; Podocyte