Biomol Ther.  2014 Sep;22(5):400-405. 10.4062/biomolther.2014.035.

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies

• Kim S
• Kim DH
• Kim YS
• Ha TY
• Yang J
• Park SH
• Jeong KW
• Rhee JK

• KMID: 2380316
• DOI: http://doi.org/10.4062/biomolther.2014.035

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.

Keyword

GPR119 agonist; Type 2 diabetes; GLP-1

MeSH Terms

Animals
Blood Glucose
Diabetes Mellitus, Type 2
Glucagon-Like Peptide 1
Glucose Tolerance Test
GTP-Binding Proteins
Humans
Insulin
Mice
Plasma
Rodentia
Blood Glucose
GTP-Binding Proteins
Glucagon-Like Peptide 1
Insulin