Figure 1.
Liraglutide and exendin-4 are effective weight management drugs in high fat-fed C57BL/6 mice, but liraglutide is more effective at improving glucose tolerance.
The weight of male C57BL/6 mice was monitored on a weekly basis over a period of eight weeks (white area) on high fat (HFD) or normal chow diet (ND), followed by 75 days (grey area) of daily intraperitoneal injections of saline, or a GLP-1 mimetic- liraglutide (panels A–C), exendin-4 (panels D–F), or sitagliptin (panels G–I). Intra-peritoneal glucose tolerance tests were performed after 75 days of treatment (B–C, E–F, H–I). Time courses (B, E, H) and the corresponding areas under the curve (C, F, I) are shown. p≤0.001, ***; p≤0.01, **, n = 3–7 mice.
Figure 2.
Long term adminstration of exendin-4, liraglutide and sitagliptin exerts different effects on beta-cell mass but no effect on alpha-cell mass.
Representative images of pancreatic sections stained for insulin (green), glucagon (red) and nuclei (DAPI, blue) (A). Pancreatic sections from mice treated with liraglutide (B, E), exendin-4 (C, F) and sitagliptin (D, G) were examined. Beta-cell mass (B, C, D), and alpha-cell mass (E, F, G) were measured from whole section scans as described in ‘Materials and Methods’. p≤0.001, ***; p≤0.01, n = 3–7 mice.
Figure 3.
C57BL/6 mice do not display clinical signs of pancreatitis following 75 days' treatment with liraglutide, exendin-4, or sitagliptin.
Reg3b immunoreactivity was assessed in pancreatic sections from mice treated with saline (Ai), liraglutide (B), exendin-4 (Aii, C) and sitagliptin (D), and normalised to Reg3b area observed in pancreata from saline treated mice, as described in ‘Materials and Methods’. Plasma amylase (E) and lipase (F) levels were measured after 75 days treatment with saline, liraglutide, exendin-4 or sitagliptin. ND, normal chow diet; HFD, high fat diet. p≤0.05, *; p≤0.01, **, n = 3–7 mice.