They discover a key mechanism in the regulation of glucose production in the liver

The maintenance of glucose levels (Sugar) in the blood requires a series of coordinated mechanisms in response to the availability or lack of food. So, during fasting, glucose is produced prevent excessive dropping (hypoglycaemia) while post-meal glucose production is inhibited to prevent this its uncontrolled excess (hyperglycemia).

The liver plays a key role in this process large glucose producer from the body. Now the Molecular Metabolism group led by the University of Santiago de Compostela (USC) has just discovered a new key mechanism in the regulation of glucose production in the liver: nedilation.

According to the WHO, diabetes is the seventh leading cause of death worldwide.

The work that just got published in the journal cellular metabolismopens the way to it new therapeutic approaches for the onset of diabetes, which according to the World Health Organization (WHO) is the seventh cause of death worldwide.

Advances in Diabetes

The necessary regulation of hepatic glucose production does not work properly in people with diabetesa disease in which the body does not produce enough insulin (type 1 diabetes) or does not use the insulin it produces properly (type 2 diabetes), causing blood sugar levels to rise and which over time can lead to diabetes serious health problems B. Diseases of the heart, kidneys or arterial hypertension.

In molecular biology it is known as post-translational modification on what the molecules that are added to proteins do to change their properties, for example by affecting their activity, their cellular localization or their ability to interact with other proteins.

Nedilation is an essential mechanism for regulating hepatic glucose production, both during fasting and after eating.

“Nedilation is one of those post-translational modifications that consists of adding a small protein called NEDD8 to the target proteins. In contrast to other molecular mechanisms that have been studied for many years and are very well defined, nedilation and its functions are still present are largely unknown“, explains the USC researcher Mary Jesus Gonzalez Rellanfirst author.

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“In particular, their functions have been studied in certain pathological contexts, such as in liver cancer and fibrosiswhere this post-translational modification stabilized proteins that favored disease progression,” he states.

The article mentions nedilation as “an essential mechanism for regulate glucose production in the liver, during fasting and after eating,” explains the expert. “The hepatic levels of the proteins NEDD8 and NAE1 (enzyme responsible for nedilation) increase dramatically during fasting This allows the liver to produce glucose.”

This study also “describes for the first time that nedilation regulates the activity of.” Phosphoenolpyruvate carboxykinase 1 (PCK1), one of the most important proteins in the process of glucose production in the liver, and to which no type of modification has been ascribed a determining role in regulating its activity,” argues the co-first author, Uxia Fernández Paz.

The work also shows that hepatic edilation levels are elevated Patients with type 2 diabetes. This fact represents an advance in the study of pathology, as it offers an entirely new and unexpected perspective on how it is regulated. glucose production in the liverIt also offers a tool to control and reduce PCK1 activity and therefore the high glucose levels typical of diabetics.

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