Researchers at the University of Santiago de Compostela (USC) have discovered through research that the p53 protein is responsible for regulating glucose production in the organism and is therefore responsible for blood glucose levels in the organism.
Furthermore, these researchers have found that this protein is altered in patients with diabetes. On the other hand, previous research had already confirmed a protective role of the p53 protein against cancer.
Specifically, this study was conducted by researchers from the Molecular Metabolism group of CiMUS at the University of Santiago de Compostela (USC); also attached to the CIBER of Obesity and Nutrition (CIBEROBN), in collaboration with other research groups from Cic BIOGUNE, CNIC, the University Clinic of Navarra; as well as international groups from Germany, Switzerland, Norway and Korea.
The p53 protein as a regulator of glycemia
This is a broad study of a protein that has been extensively studied in the field of oncology due to its different functions as a tumor suppressor. However, its possible participation in hepatic glucose production under physiological conditions had not been analyzed so far.
CiMUS researcher María J. González Rellán explains how the p53 protein is a key factor in hepatic glucose production during fasting: «Under these conditions, p53 undergoes a post-transcriptional modification, called O-GlcNAcylation, which promotes its stabilization and allows it to promote the expression of PCK1, one of the most important enzymes involved in glucose production».
In this sense, these researchers have detailed the way in which the main hormones that enhance glucose production require O-GlcNAcylation of p53 in order to induce glucose production.
In this regard, this specialist points out that «on the contrary, an excessive increase in the levels of O-GlcNAcylated p53 prevents insulin signaling from acting appropriately in the liver, generating insulin resistance».
Therefore, this discovery in relation to the p53 protein could open up a new panorama in terms of glycemic control in the organism and potential treatments for patients with diabetes.
This study shows that the levels of enzymes involved in O-GlcNAcylation and levels of p53 and PCK1 are significantly increased in the liver of patients with type 2 diabetes. Thus, the researchers suggest that this is a major breakthrough for the study of the pathology.
It really brings a completely different and unexpected new approach and insight into how glucose production is regulated in the liver. It is a determining factor in blood glucose levels.
Diabetes, the seventh leading cause of death worldwide
Currently, around one in 11 adults in the world has diabetes, according to the estimate made by the World Health Organization (WHO). This organization has ranked diabetes as the seventh leading cause of death worldwide.
Thus, the maintenance of blood glucose levels requires the correct functioning of a series of mechanisms. In this regard, during fasting, the organism tends to produce different amounts of glucose to prevent any episode of hypoglycemia (low blood glucose levels). After meals, glucose production slows down to prevent possible hyperglycemia.
This is where the p53 protein plays a key role, since the main glucose producer in the organism is the liver.
