HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies
Biomolecules & Therapeutics
;
: 400-405, 2014.
Artigo
em Inglês
| WPRIM
| ID: wpr-145967
ABSTRACT
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 beta-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic beta-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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Plasma
/
Roedores
/
Glicemia
/
Proteínas de Ligação ao GTP
/
Diabetes Mellitus Tipo 2
/
Peptídeo 1 Semelhante ao Glucagon
/
Teste de Tolerância a Glucose
/
Insulina
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Biomolecules & Therapeutics
Ano de publicação:
2014
Tipo de documento:
Artigo
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