a, Representative hematoxylin and eosin (H&E) staining from liver tissue sections. Scale bars, 100 μm or 50 μm. The rectangular frame indicates the area displayed at a higher magnification. b, c, Hepatic TG (b), and T-CHO (c) levels of db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. d, e, Hepatic levels of IL-1β (d) and TNF-α (e) in db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. f-i, Ameliorating effect of GIFT GLP-1 on oxidative stress in diabetic mouse liver. After 30 days of treatment with PBS, GIFT Lux , or GIFT GLP−1 , livers of db/db mice were harvested and homogenized. The levels of oxidative stress markers were measured, including MDA (f), SOD (g), GSH (h), and T-AOC (i). j, k, Renal levels of IL-1β (j) and TNF-α (k) in db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. l-o, Ameliorating effect of GIFT GLP-1 on oxidative stress in diabetic mouse kidney. After 30 days of treatment with PBS, GIFT Lux , or GIFT GLP-1 , the kidneys of db/db mice were harvested and homogenized. The levels of oxidative stress markers were measured, including MDA (l), SOD (m), GSH (n), and T-AOC (o). p-u, Effect of GIFT GLP-1 on alleviating renal damage. After 30 days of treatment with PBS, GIFT Lux , or GIFT GLP-1 , serum levels of creatinine (CRE) (p), blood urea nitrogen (BUN) (q), and urine protein (r) in db/db mice were measured. Kidneys were harvested and weighed, and the kidney-to-body weight ratios (s) were calculated. Histopathological analyses of kidney sections, including H&E staining, Masson’s trichrome staining, and PAS staining (t), were performed. Scale bars, 50 μm. u, Masson’s trichrome staining to quantify glomerular fibrosis (20 glomeruli per mouse were analyzed, n = 5 mice per group). v, w Colonic IL-1β (v), and TNF-α (w) levels of db/db mice treated with PBS, GIFT Lux , or GIFT GLP-1 for 30 days. x, Representative H&E staining from colon tissue section. Scale bars, 100 μm. Representative images from three independent experiments with similar results are shown in a, t, x. Data in b-e, j, k, p-s, u-w are expressed as means ± s.e.m.; n = 5 mice. For box-and-whisker plots in f-i, l-o, the centre line denotes the median, the box bounds indicate the 25th and 75th percentiles, and the whiskers extend from the minimum to maximum values. P-values in b-s, u-w were calculated using one-way ANOVA followed by Tukey’s multiple comparisons test. NS, not significant; *P < 0.05, **P < 0.01, ***P < 0.001. Detailed statistics are provided in Supplementary Table 16.
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