The hypothesis for the research study was “The connection of p53 activity and p53 Ser18 phosphorylation to metabolic regulation supports a model whereby the mechanism of ATM-mediated physiological regulation of insulin sensitivity may involve p53 activity and ATM-mediated p53 phosphorylation” (Heather, Armata, Golebiowski, Young, Jin Ko, Jason, Kim, and Sluss 3). To test the above hypothesis the metabolic control in mice was compared in presence and absence of a germ line mutation in p53 phosphorylation site Ser18.
These p53 mice shows defects in p53-mediated apoptosis and gene expression (Heather 10), but unlike p53-null mice, p53 mice cultivate tumors lone at advanced age (Heather 1). Scrutiny of the different metabolic considerations showed that p53 mice haveraised metabolic stress. This metabolic deregulation is probable of mediating through raised levels of ROS, as antioxidant treatment refurbishes insulin sensitivity. In fact, we perceived compromised glucose homeostasis and insulin resistance in the specimen animals, showingthat p53 Ser18 takes part in a metabolic checkpoint.
The research was carried out to analyse and demonstrate how p53 phosphorylation when exposed on an ATM site it can form a vital mechanism in the physiological regulation of glucose homeostasis (Heather & others1). Ataxia telangiectasia (A-T) patients are known to get infected with a number of clinical pathologies which include growth hindrance, neuronal degeneration, and increased chances of contacting cancer as well as telangiectasias. The stated patients are also known to show an elevated risk of developing type 2 diabetes and insulin resistance. This research shows how the ATM protein kinase- a product of gene mutated A-T patients- has been drawn in in metabolic disease, which is described by insulin resistance and elevated cholesterol and lipid levels, blood pressure, and atherosclerosis ((Heather & others 3). To find out if the ATM pathway that controls insulin resistance is arbitrated by p53 phosphorylation, insulin sensitivity was inversgated in mice that was characterized by a germ line mutation comes in place of p53 phosphorylation site that contains alanine. After the test the forfeiture of p53 resulted into raised metabolic stress that was part of the severe weaknesses in glucose homeostasis. Therefore the mice showed development of insulin resistance as well as glucose intolerance. The insulin resistance was linked to the loss of antioxidant gene manifestation and reduced insulin signaling.
The methodology that was employed in the research to ascertain the validity of the hypothesis is to conduct a glucose and insulin tolerance test. The methodology that was used to ascertain the hypothesis was the metabolic control in mice which was compared in presence and absence of a germ line mutation in p53 phosphorylation site Ser18. The hypothesis for the research study was “The connection of p53 activity and p53 Ser18 phosphorylation to metabolic regulation supports a model whereby the mechanism of ATM-mediated physiological regulation of insulin sensitivity may involve p53 activity and ATM-mediated p53 phosphorylation.” The methodology that was used was effective in that it confimed the hypotheis. The results reveal that “It has been reported that p53 can regulate the expression of the synthesis of the cytochrome c oxidase 2 gene (Sco2), which is required for mitochondrial respiration. We examined Sco2 expression and found no difference between p53S18A and wild-type fibroblasts. There was no significant difference in p53 expression between p53S18A and wild-type fibroblasts (data not shown). Thus, increased ROS levels in p53S18A fibroblasts may not be due to defective mitochondrial function.”
The results shows that treatment of p53S18A mice leads to restoration of glucose tolerant but the observation reveals that in wild mice will remain unchanged. However, it is important to take note of the fact that its role in AMPK-mediated response is actually not clear. It is important that more research is taken into consideration so that measures are put in place to ensure that a clear cut and a precise relationship between AMPK-mediated response is actually is addressed to be clear. Moreover, it is important that the discussion section breaks down critical points so that they are easily comprehended by the users of the research paper. It is critical that measures are put in place to ensure that the discussion and analysis of the results are simplified for the sake of end users.
In conclusion, it is worth noting that the research is reliable and valid owing to the fact that the methodology used to collect the data was succinct. Moreover, results have confirmed the original hypotheis for this study. The hypothesis for the research study was “The connection of p53 activity and p53 Ser18 phosphorylation to metabolic regulation supports a model whereby the mechanism of ATM-mediated physiological regulation of insulin sensitivity may involve p53 activity and ATM-mediated p53 phosphorylation.” Despite the few flawsa that were inherent in the research it is worth noting that the results and the research in general is good and any academician or student who wishes to gain further information on how to collect data will find it useful.
Work Cited
Heather, L, Armata, D. Golebiowski, D. Young, H. Jin Ko, K. Jason, Kim, and H. K. Sluss. "Requirement of the ATM/p53 Tumor Suppressor Pathway for Glucose Homeostasis▿."American Association of Microbiology 30.24 (2010): 5787-5794. Web. 1 Dec. 2013.
