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19 May 2018 : Animal Research

Comparative Study of Liraglutide and Insulin Glargine on Glycemic Control and Pancreatic β-Cell Function in db/db Mice

Yanli Li1DEF*, Jia Zheng2CDE, Yunfeng Shen34A, Wangen Li1AG, Meimei Liu5BC, Jun Wang3BC, Surong Zhu3BC, Meihua Wu3BC

DOI: 10.12659/MSM.907227

Med Sci Monit 2018; 24: ANS3293-3300

Abstract

BACKGROUND: The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice.

MATERIAL AND METHODS: Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8–14 weeks-of-age. Body weight, pancreatic weight, levels of blood glucose, triacylglycerol, C-peptide, and the intraperitoneal glucose tolerance test (IPGTT) were used. Expression levels of the INS1 gene were measured using reverse transcription polymerase chain reaction (RT-PCR), and pancreatic and duodenal homeobox 1 (Pdx1), paired box 4 (Pax4), and paired box 6 (Pax6) mRNA expression were measured.

RESULTS: Both insulin glargine and liraglutide improved glycemic control of db/db mice when compared with vehicle. The following were significantly increased in the HLG compared with the GG: the receiver operating characteristic (ROC) area under the curve (AUC) for the IPGTT; C-peptide levels; the pancreas to body weight coefficient; expression levels of the INS1 gene and pancreatic transcription factors Pdx1, Pax4 and Pax6. Liraglutide treatment was without hypoglycemic effects.

CONCLUSIONS: Liraglutide acted in a dose-dependent manner on glycemic control of db/db mice, and was more effective than insulin glargine, when administered at a high dose.

Keywords: Diabetes Mellitus, Glucagon-Like Peptide 1, Insulin, Insulin-Secreting Cells

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750