Molecular MedicineMetabolic engineering and diabetes therapy

Metabolic engineering and diabetes therapy

The group directed by Prof. Guinovart is involved in several projects on glycogen metabolism and its dysfunctions in diabetes and Lafora disease. Studies on glycogen metabolism have allowed the identification of many enzymes and intermediate metabolites involved in the synthesis and degradation of this polysaccharide. However, new factors and processes that participate in glycogen regulation are constantly being discovered. Moreover, data on the mechanisms of control in distinct organs and in diverse physiological conditions are incomplete. The alteration of one of these mechanisms may lead to serious pathologies such as diabetes mellitus and Lafora disease. The discovery of compounds that counteract the alterations of glucose metabolism is of potential interest for the treatment of diabetes mellitus.

  • To study the mechanisms of glucose storage in the form of glycogen in liver, muscle and brain and its alterations in diabetes and neurological disorders.
  • To identify and characterize novel compounds with anti-diabetic action.
  • To identify novel potential molecular targets for the design of anti-diabetic compounds.

1) To characterise the physiological role of glycogen in the CNS and in particular in neurons.

Main tasks:

a) To study the molecular changes associated with the lack of glycogen in the brain.

b) To further demonstrate the presence of glycogen in neurons and analyse its role in the normal functioning of this cell type.

 

2) To study the pathological consequences of neuronal glycogen accumulation in pathological conditions and aging.

Main tasks:

a) To further examine the molecular mechanism(s) of neurodegeneration induced by the accumulation of glycogen.

b) To address the reversibility of abnormal glycogen accumulation in Lafora disease.

c) To study the role of neuronal glycogen accumulation in the etiopathogeny of ALS, diabetic complications, and aging.

 

3) To analyse the consequences of abnormal accumulation of glycogen in muscular glycogenoses.

Main tasks:

a) To study the consequences of the over-accumulation of glycogen in skeletal muscle.

b) To examine the contribution of glycogen accumulation in neurons to the physiopathology of Pompe disease.

 

4) To analyse the role of hepatic glycogen in feeding behaviour.

Main tasks:

a) To study how the amount of liver glycogen regulates food intake.

b) To determine hepatic ATP involvement in food intake.

 

5) To revisit the role of glycogenin in glycogen synthesis.

Main tasks:

a) To characterise an animal model lacking glycogenin (GYG).

b) To study other possible functions of GYG besides glycogen initiation.

 

Testoni G, Duran J, García-Rocha M, Vilaplana F, Serrano AL, Sebastián D, López-Soldado I, Sullivan MA, Slebe F, Vilaseca M, Muñoz-Cánoves P and Guinovart JJ.
Cell Metab, 26 (1), 256-266.e4 (2017)
Slebe F, Rojo F, Vinaixa M, García-Rocha M, Testoni G, Guiu M, Planet E, Samino S, Arenas EJ, Beltran A, Rovira A, Lluch A, Salvatella X, Yanes O, Albanell J, Guinovart JJ and Gomis RR.
Nat Commun, 7 11199 (2016)
López-Soldado I, Zafra D, Duran J, Adrover A, Calbó J and Guinovart JJ.
Diabetes, 64 (3), 796-807 (2015)
Sinadinos C, Valles-Ortega J, Boulan L, Solsona E, Tevy MF, Marquez M, Duran J, Lopez-Iglesias C, Calbó J, Blasco E, Pumarola M, Milán M* and Guinovart JJ*
Aging Cell, 13 (5), 935-945 (2014)
Saez I, Duran J, Sinadinos C, Beltran A, Yanes O, Tevy MF, Martínez-Pons C, Milán M and Guinovart JJ.
J Cerebr Blood F Met, 34 (6), 945-55 (2014)
Duran J, Gruart A, García-Rocha M, Delgado-García JM and Guinovart JJ.
Hum Mol Genet, 23 (12), 3147-56 (2014)
Duran J, Saez I, Gruart A, Guinovart JJ and Delgado-García JM.
J Cerebr Blood F Met, 33 (4), 550-6 (2013)
Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M* and Guinovart JJ*.
EMBO Mol Med, 4 (8), 719-29 (2012)
Valles-Ortega J, Duran J, Garcia-Rocha M, Bosch C, Saez I, Pujadas L, Serafin A, Cañas X, Soriano E, Delgado-García JM, Gruart A and Guinovart JJ.
EMBO Mol Med, 3 (11), 667-81 (2011)

* shared senior authorship

This group receives financial support from the following sources:

  • Instituto de Salud Carlos III. Ministerio de Sanidad y Consumo (Spanish National Institute of Health)
  • Fundació “La Caixa” ("la Caixa" Foundation)
  • Ministerio de Educación y Ciencia (Spanish Ministry of Education and Science)
  • Fundación Marcelino Botín (M. Botín Foundation)
  • Marató de TV3
  • Ministerio de Economía y Competitividad (MINECO)
  • European Commission (EC), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa"

     

Group news & mentions

<p>Glycogen (black particles) accumulates in large amounts in the muscle due to the absence of the protein glycogenin (Giorgia Testoni, IRB Barcelona)</p>
9 Jul 2017

The Bulgarian news website Nauka Offnews, among other media outlets, has echoed on the study performed by IRB Barcelona scientists on glycogen synthesis and high glycogen levels in mice.

<p>Glycogen (black particles) accumulates in large amounts in the muscle due to the absence of the protein glycogenin (Giorgia Testoni, IRB Barcelona)</p>
6 Jul 2017

In 2009, Usain Bolt set the world record in the 100-meter dash, thanks in large part to a carb called glycogen.

<p>"La Marató" (telethon) has awarded two IRB Barcelona research projects in diabetes and obesity</p>
18 May 2017

Catalonia's public television channel, TV3, has broadcasted various video abstracts that give scientists the opportunity to explain their research funded by the telethon (La Marató) run by the Cata

<p>Open Day 2015.</p>
8 May 2017

Discovering how to use a microscope built with Lego blocks and take photos with a mobile phone, making "cellular spheres", and eating ice cream made with liquid nitrogen are some of the multiple ac

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