FIGURE 1.

Hexosamine biosynthetic pathway activation by GlcNAc feeding does not have adverse effects in mice. (a) Schematic representation of the hexosamine biosynthetic pathway. The rate‐limiting enzyme glutamine fructose‐6‐phosphate amidotransferase (GFAT) is depicted in purple, GlcNAc is marked in blue. GNPDA: Glucosamine‐6‐phosphate isomerase 1; GNA1: Glucosamine‐6‐phosphate N‐acetyltransferase; PGM3: Phosphoacetylglucosamine mutase; UAP1: UDP‐N‐acetylhexosamine pyrophosphorylase; GALE: UDP‐glucose 4‐epimerase; HK: Hexokinase; NAGK: N‐acetyl‐D‐glucosamine kinase. (b) Drinking volume of control (white) and GlcNAc‐treated mice (blue) of both sexes at 3 and 9 months of age. Data are presented as mean ± SD (n ≥ 7). Two‐way ANOVA, Tukey's post‐test; *p < 0.05; ns: Not significant. (c) GlcNAc consumption in mg/kg body weight per day of mice of both sexes at 3 and 9 months of age. Data are presented as mean ± SD (n ≥ 7). Unpaired t‐test; ns: Not significant. (d) Relative UDP‐HexNAc levels in hemibrains of control (white) and GlcNAc‐treated mice (blue) of both sexes. Data are presented as mean ± SEM (n = 6). Unpaired t‐test; ns: Not significant. (e) Blood glucose concentration at 0 (fasting), 15, 30, 60, and 120 min after intraperitoneal injection of glucose solution (2 g/kg body weight) of control (black) and GlcNAc‐treated mice (blue) of both sexes at 10 months of age. Data are presented as mean ± SD (n ≥ 7). Multiple unpaired t‐tests; ns: Not significant (f) area under the curve (AUC) calculated using data shown in (e). Data are presented as mean ± SD (n ≥ 7). Unpaired t‐test; ns: Not significant (g) Body weight of control (black) and GlcNAc‐treated mice (blue) of both sexes from 3 to 30 months of age. The data point at 19 months (females) is missing since the body weight measurements were not performed for this time point. Data are presented as mean ± SD (n ≥ 13). Multiple unpaired t‐tests; **p < 0.01; *p < 0.05; only significant changes are indicated