Overexpression of p53 Improves Blood Glucose Control in an Insulin Resistant Diabetic Mouse Model. Issue 7 (August 2016)

• Record Type: Journal Article
• Authors: Zhang, Xuemei; Duan, Wei; Lee, Wai-Nang Paul; Zhang, Yuewei; Xiang, Fenfen; Liu, Qian; Go, Vay Liang W.; Xiao, Gary Guishan
• Is Part Of: Pancreas. Volume 45:Issue 7(2016)
• Publication Date: 2016-08
• Subjects: recombinant human adenoviral-p53 gene -- glucose metabolism -- insulin resistance -- STZ/high-fat-diet diabetic mouse model -- Fbp1 - fructose-1, 6-bisphosphatase -- G6pc - glucose-6-phosphatase -- GK - glucose kinase -- GLUT2 - glucose transporter 2 -- GP - glycogenphosphorylase -- GS - glycogen synthase -- HFD - high-fat diet -- InsR - insulin receptor β -- IPGTT - intraperitoneal glucose tolerance test -- PP-1 - protein phosphatase-1 -- PPAR-γ - peroxisome proliferator-activated receptor γ -- rAd-p53 - recombinant adenoviral p53 -- ROS - reactive oxygen species -- STZ - streptozotocin -- TC - total cholesterol -- TG - triglyceride -- TIGAR - TP53-induced glycolysis and apoptosis regulator -- TP53 - tumor protein p53 gene -- VP - viral particles; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000000637
• Languages: English
• ISSNs: 0885-3177

Abstract

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. Abstract : Supplemental digital content is available in the text.