Extended Data Fig. 6: Assessment of MK-801 as a half-life extender of gut peptide hormones.
From: GLP-1-directed NMDA receptor antagonism for obesity treatment
a-c, Treatment of DIO mice with once-daily s.c. injections of 100 nmol kg−1 GIP analogue (n = 8 mice and n = 4 cages), 100 nmol kg−1 GIP–MK-801 (n = 8 mice and n = 4 cages) or vehicle (isotonic saline, n = 8 mice and n = 4 cages) for 7 days. a, Schematic. b, Change in body weight. c, Cumulative food intake. d, In vitro stability assay of GIP–MK-801 (n = 2) incubated in human plasma or PBS, pH = 7.4 (n = 1). e-g, Treatment of DIO mice with once daily s.c. injections of 100 nmol kg−1 PYY analogue (n = 7 mice and n = 6 cages), 100 nmol kg−1 PYY–MK-801 (n = 7 mice and n = 4 cages), 100 nmol kg−1 GLP-1–MK-801 (n = 7 mice and n = 5 cages) or vehicle (isotonic saline, n = 7 mice and n = 4 cages) for 6 days. The dose of PYY-based compounds was escalated at day 4 from 100 nmol kg−1 to 500 nmol kg−1. e, Schematic. f, Change in body weight. g, Cumulative food intake. h-j, Treatment of DIO mice with once daily s.c. injections of 50 nmol kg−1 GIP/GLP-1 (n = 6 mice and n = 3 cages), 50 nmol kg−1 GIP/GLP-1–MK-801 (n = 6 mice and n = 3 cages) or vehicle (isotonic saline, n = 6 mice and n = 3 cages) for 5 days. h, Schematic. i, Change in body weight. j, Cumulative food intake. k, In vitro stability assay of GIP/GLP-1–MK-801 (n = 3) incubated in human plasma. Data analysed by two-way repeated measures ANOVA to assess main effects of treatment (b, c, f, g, i and j). Data represents mean ± SEM; *P < 0.05, ****P < 0.0001. Detailed statistics are in Supplementary Table 1 and chemical structures are in Supplementary Fig. 1. The diagrams in a, e and h were created using BioRender.