title: Gemigliptin, a novel dipeptidyl peptidase-4 inhibitor, exhibits potent anti-glycation properties in vitro and in vivo.
abstract: This study evaluated the inhibitory effects of gemigliptin, a highly selective dipeptidyl peptidase-4 inhibitor, on the formation of advanced glycation end products (AGEs) and AGE cross-links with proteins in in vitro as well as in type 2 diabetic db/db mice. In in vitro assay, gemigliptin dose-dependently inhibited methylglyoxal-modified AGE-bovine serum albumin (BSA) formation (IC50=11.69 mM). AGE-collagen cross-linking assays showed that gemigliptin had a potent inhibitory effect (IC50=1.39 mM) on AGE-BSA cross-links to rat tail tendon collagen, and its activity was stronger than aminoguanidine (IC50=26.4 mM). In addition, gemigliptin directly trapped methylglyoxal in a concentration-dependent manner in vitro. To determine whether gemigliptin inhibits the in vivo glycation processes, gemigliptin (100 mg/kg/day) was orally administered into type 2 diabetic db/db mice for 12 weeks. Elevated serum levels of AGEs in db/db mice were suppressed by the administration of gemigliptin. These inhibitory effects of gemigliptin on the glycation process in both in vitro and in vivo suggest its therapeutic potential for ameliorating AGE-related diabetic complications.
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, Republic of Korea; LG Life Sciences Ltd., R&D Park, Daejeon 305-343, Republic of 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, Republic of Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
authors.affiliation: LG Life Sciences Ltd., R&D Park, Daejeon 305-343, Republic of Korea.
authors.forename: Sung Ho
authors.initials: SH
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, Republic of 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, Republic of Korea; Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 151-742, Republic of Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 443-270, Republic of Korea. Electronic address: mchotox@snu.ac.kr.
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010881:Piperidones / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007004:Hypoglycemic Agents; C534891:LC15-0444; D010881:Piperidones; D011743:Pyrimidines; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D003094:Collagen; D018819:Dipeptidyl Peptidase 4; C004479:pimagedine
keywords: Advanced glycation end products (AGEs); Gemigliptin; Gemigliptin (PubChem CID: 11953153); Glycation; Methyglyoxal; Saxagliptin (PubChem CID: 11243969); Vildagliptin (PubChem CID: 11077541)