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However, the precise function and mechanism of action of p53 in the regulation of glucose\u2010lipid metabolism through the enterohepatic axis remain to be fully elucidated. The present study investigated the effects of p53 deficiency on type 2 diabetic mice and demonstrated that p53 deficiency resulted in more severe impairment of glucose tolerance and insulin tolerance. Furthermore, the study revealed that p53 can influence hepatic glucose metabolism via the PI3K\/AKT pathway. Additionally, p53 deletion has been observed to modify intestinal function and the intestinal microenvironment, thereby correlating with intestinal function and microbiota composition in T2DM mice. Specifically, p53 knockout mice exhibited impaired ileal digestion, absorption, and colonic secretion after a HFD (HFD). Additionally, the richness and diversity of their intestinal microbiota were reduced, and these mice exhibited symptoms such as obesity, fat infiltration, defecation abnormalities, and severe abnormalities of glucose and insulin tolerance. The expression levels of \u03b2\u2010catenin and c\u2010Myc proteins were found to be elevated in mice fed a HFD, while the expression of these proteins was diminished in mice with p53 knockout, compared to those on a normal diet. 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