Overexpression of p53 Improves Blood Glucose Control in an Insulin Resistant Diabetic Mouse Model.
This paper aimed to assess the physiological effects of p53 on glucose homeostasis in vivo.



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.



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.



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.
From the *The Medical College of Dalian University, Dalian Economic and Technical Development Zone; †Affiliated Zhongshan Hospital of Dalian University, Dalian, China; ‡Metabolomics Core, LA Biomed, David Geffen School of Medicine, University of California Los Angeles, Torrance; §Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA; ∥School of Pharmaceutical Science and Technology at Dalian University of Technology, Dalian, China; and ¶Department of Medicine and Medical Microbiology, Creighton University, Omaha, NE.
Xuemei
X
Zhang
Wei
W
Duan
Wai-Nang Paul
WN
Lee
Yuewei
Y
Zhang
Fenfen
F
Xiang
Qian
Q
Liu
Vay Liang W
VL
Go
Gary Guishan
GG
Xiao
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D015153:Blotting, Western; D002096:C-Peptide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000209:etiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000235:genetics*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D005943:Gluconeogenesis / Q000235:genetics; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D001786:Blood Glucose; D002096:C-Peptide; D051273:Glucose Transporter Type 2; D007328:Insulin; D047495:PPAR gamma; C495682:Slc2a2 protein, mouse; D014280:Triglycerides; D016159:Tumor Suppressor Protein p53