The free fatty acid receptor 1 (FFAR1/GPR40) mediates fatty acid-dependent augmentation of glucose-induced insulin secretion (GIIS) in pancreatic β-cells. The objective of the studies described here was to examine the pharmacological properties of HD-6277 in cell based assay and preclinical models of T2D. Insulin secretion was evaluated in INS-1 cells, HD-6277 (0.1∼10 μM) treated group enhanced more insulin secretion than sulfonylurea added condition. HD-6277 (100 mg/kg) did not induced hypoglycemia even combinational treatment with Metformin (50 mg/kg) in Sprague-Dawley rats. Goto-Kakizaki (GK) rats have known as type 2 diabetic model with secondary failure and apoptosis of pancreatic beta-cell. HD-6277 and glimepiride were administered to GK rats of 8 (young) and 26 (old) weeks old, respectively. Glucose tolerance tests (GTT) were performed at the starting and the ending point of the chronic administration. Administration of HD-6277 and glimepiride improved glycemic control and insulin secretion, compared to vehicle control groups in young GK rats, however, chronic administration of glimepiride cause loss of glycemic control efficacy, whereas HD-6277 did not. At the end of chronic administration, glimepiride-treated group demonstrated poor glycemic control and insulin secretion during GTT than HD-6277-treated group. In administration of HD-6277 and glimepiride to old GK rats, HD-6277-treated group has showed ameliorate in glycemic control than vehicle group, however glimepiride-treated group did not.

Thus, repeated administration of HD-6277 can preserves pancreatic islets, improves beta cell function and attenuates diabetes.

Disclosure

S. Kang: Employee; Self; Hyundai Pharm. corp. C. Kim: Employee; Self; Hyundai Pharm. corp.. H. Choi: None. G. Yang: Employee; Self; Hyundai Pharm. CORP. S. Lee: Employee; Self; Hyundai Pharm. CORP. K. Lim: Employee; Self; Hyundai Pharm. corp. M. Park: Employee; Self; Hyundai Pharm.corp. D. Kim: Employee; Self; Hyundai Pharm. CORP. J. Yang: Employee; Self; Hyundai Pharm. corp. J. Rhee: Employee; Self; Hyundai Pharm. corp. D. Kim: Employee; Self; Hyundai Pharm. Corp..

© 2018 by the American Diabetes Association.
2018
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