Role of Tumor Suppressor P53 Family in Glucose Metabolism in Association with Diabetes

Abstract

Subsequent manuscripts have shown that p53, a 391 amino acid protein, was associated with tumour suppression by inducing cell cycle arrest, senescence, or programmed cell death, and mainly focused on oncology. But recent studies are proclaiming that the p53 family of genes is also associated with regulating the balance of the glucose uptake via the many glucose transporters by directly repressing the expression of the GLUT1 & GLUT4, use of glycolysis and oxidative phosphorylation. The p53 regulates phenotypes of diabetes as it is interjecting in many points in regulating the pancreatic function and apoptosis, dysregulation of the beta cells, and developing insulin resistance. In the context of pancreatic beta cells, which are functioning for insulin secretion, it is regulated by the p53 by multiple signalling pathways. Endoplasmic stress results in the accumulation of the p53 that interacts with PARK2 (parkin), leading to insulin deficiency. Additionally, several proteins (N-terminal truncated isoforms of p53, factor TCFL2, the microRNA miR 200) regulate the p53 pathway, which can also regulate its ability to mediate pancreatic beta cell death. While in glucose haemostasis, wild-type p53 negatively and mutant p53 positively regulate glucose transporters and glucose importers. P21/CDKNIA plays an important role in developing insulin resistance as the p53-mediated senescence of adipose tissue marks it. Also, excessive O-GLcynated p53 inhibits the insulin signalling pathway from acting on the liver, generating insulin resistance. Here, we present a literature review on the role of p53 in metabolism, diabetes, pancreatic function, glucose homeostasis, and insulin resistance. Interestingly, mutations in the p53 gene were shown to occur at different phases of the multistep process of malignant transformation.