Overexpression of p53 Improves Blood Glucose Control in an Insulin Resistant Diabetic Mouse Model

Abstract

Objective This paper aimed to assess the physiological effects of p53 on glucose homeostasis in vivo. Methods A recombinant adenoviral p53 (rAd-p53) vector was administered to insulin-resistant diabetic mice. Intraperitoneal glucose tolerance test was performed in all groups of mice. Changes in fasting blood glucose, serum triglycerides, C-peptide, and insulin concentrations in treated and untreated mice were measured. Analyses of the target genes related to glucose metabolism were performed. Results Treatment with the rAd-p53 improved glucose control in a dose- and time-dependent manner and lowered significantly the fasting blood glucose, the serum triglycerides, and improved tolerance test of glucose as compared to control. Lowered blood glucose was associated with up-regulation of genes in the glycogenesis pathways, and down-regulation of genes in the gluconeogenesis pathways in the liver. Overexpressions of GLUT2, GK, PPAR-γ, and insulin receptor precursor were also observed in the liver and the pancreas of treated animals. Conclusions Activation of p53-mediated glucose metabolism led to insulin-like antidiabetic effect in the mouse model especially by changing hepatic insulin sensitivity in the diabetic mouse model.