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KMID : 0606920140220050400
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Biomolecules & Therapeutics
2014 Volume.22 No. 5 p.400 ~ p.405
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HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies
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Kim So-Ra
Kim Dae-Hoon
Kim Young-Seok
Ha Tae-Young
Yang Jin
Park Soo-Hyun
Jeong Kwang-Won
Rhee Jae-Keol
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Abstract
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G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic β-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic β-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.
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KEYWORD
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GPR119 agonist, Type 2 diabetes, GLP-1
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