Discovery of a new mechanism in the development of diabetes

Researchers from CIC bioGUNE, CIBEREHD and CiMUS discover neddylation as a key mechanism in regulating the levels of key proteins in diabetes.

The recent study, published in the international journal Cell Metabolism, reveals the critical role of neddylation as a key modulator of glucose metabolism during nutritional stress conditions.

A collaborative study at a national and international level, led by the Liver Disease laboratory, directed by Dr. Malu Martínez-Chantar (CIC bioGUNE – member of BRTA -, CIBER of Liver and Digestive Diseases - CIBEREHD), and the team from the "Molecular Metabolism" , led by Dr. Rubén Nogueiras, from the Center for Research in Molecular Medicine and Chronic Diseases (CIMUS) at the USC, has identified a dysregulation of the neddylation mechanism in patients with type 2 diabetes.

In the liver of these patients, this regulatory mechanism is abnormally induced, associated with the hyperglycemia that characterizes these individuals. The liver is one of the main organs that regulate glucose levels, which must be finely modulated both in physiological and pathological conditions, including during diabetes.

Researchers have identified that glucose modulation under nutritional stress conditions is largely mediated by neddylation. This mechanism is responsible for regulating not only the expression but also the activity of one of the main proteins responsible for glucose production in the liver, the Phosphoenolpyruvate carboxykinase PCK1.

These findings could have significant implications in the design of therapeutic approaches for diseases related to diabetes and glucose metabolism.

Reference: María J. Gonzalez-Rellan, Uxía Fernández, Tamara Parracho, Eva Novoa, Marcos F. Fondevila, Natalia da Silva Lima, Lucía Ramos, Amaia Rodríguez, Marina Serrano-Maciá, Gonzalo Perez-Mejias, Pilar Chantada-Vazquez, Cristina Riobello, Christelle Veyrat-Durebex, Sulay Tovar, Roberto Coppari, Ashwin Woodhoo, Markus Schwaninger, Vincent Prevot, Teresa C. Delgado, Miguel Lopez, Ruben Nogueiras. Cell Metabolism. DOI: 10.1016/j.cmet.2023.07.003

About CIC bioGUNE

The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.


The Consortium of Biomedical Network Research Centres (CIBER) is a public research consortium created on the initiative of the Instituto de Salud Carlos III / Carlos III Health Institute, of the Ministry of Science and Innovation, to further research of excellence in biomedicine and health sciences conducted within the National Health System and the Science and Technology System. The scientific programme of the CIBER is organised around 13 thematic areas of research, including the area of Liver Diseases (CIBEREHD) and Diabetes and Associated Metabolic Diseases (CIBERDEM).

About CiMUS

The Singular Centre for Research in Molecular Medicine and Chronic Diseases is a research centre located in Santiago de Compostela, which aims to promote the development of interdisciplinary research in the field of biomedical sciences, through internal interaction and collaboration and with relevant national and international groups.

About BRTA

BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 12 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Lortek, Neiker, Tecnalia, Tekniker and Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

Spanish version

See a large version of the first picture


Researcher Alberto Fernández Tejada obtains his third ERC Proof of Concept grant in a row

The winning project, known as ADJUPROBE, will exploit a lead adjuvant probe as...



Ikerbasque researcher from CIC bioGUNE Luca Unione obtains an European ERC Starting Grant

The European Research Council funds talented researchers who are at the beginning...