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  • Title: Gemigliptin, a novel dipeptidyl peptidase-4 inhibitor, exhibits potent anti-glycation properties in vitro and in vivo.
    Author: Jung E, Kim J, Kim SH, Kim S, Cho MH.
    Journal: Eur J Pharmacol; 2014 Dec 05; 744():98-102. PubMed ID: 25448307.
    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.
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