Molecular MedicineMetabolic engineering and diabetes therapy

Metabolic engineering and diabetes therapy

Joan J. Guinovart

Group Leader

Professor (Biochemistry and Molecular Biology Dept. - UB)

+34 93 40 37111

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) Regulation of hepatic, muscular and neuronal glycogen metabolism. Alterations in pathological conditions: diabetes mellitus and Lafora disease.

Main tasks:
a) Identification and functional analysis of the phosphorylation sites in the liver isoform of glycogen synthase.
b) Identification of the regulatory domains of glycogen synthases through structural and phylogenetic analyses.
c) Analysis of the physiological significance of the translocation of the muscle and liver isoenzymes of glycogen synthase.
d) Characterization of glycogen synthesis in neurons. Study of the components of the glycogen synthesis and degradation pathways in this cellular type.
e) Study of the alterations in glycogen metabolism in pathological situations.

  • Analysis of alterations in the post-translational modification pattern or in the subcellular localization of glycogen synthase in diabetes mellitus.
  • Study of the alterations in neuronal glycogen metabolism that lead to the production of polyglucosan bodies in Lafora disease. Involvement of laforin and malin.

2) Study of anti-diabetic agents and their possible application in diabetes treatment.

Main tasks:

  • Identification of the molecular targets of the anti-diabetic agent sodium tungstate.
  • Identification of new molecular targets for the design of anti-diabetic agents.
Duran J, Gruart A, García-Rocha M, Delgado-García JM and Guinovart JJ.
Hum Mol Genet (2014)
Rodriguez-Hernandez CJ, Llorens-Agost M, Calbó J, Murguia JR and Guinovart JJ.
Febs Lett, 10 (587), 1579-86 (2013)
Villarroel-Espíndola F, Maldonado R, Mancilla H, vander Stelt K, Acuña AI, Covarrubias A, López C, Angulo C, Castro MA, Slebe JC, Durán J, García-Rocha M, Guinovart JJ and Concha II.
J Cell Biochem, 7 (114), 1653-64 (2013)
Duran J, Saez I, Gruart A, Guinovart JJ and Delgado-García JM.
J Cerebr Blood F Met, 4 (33), 550-6 (2013)
Nocito L, Zafra D, Calbó J, Domínguez J and Guinovart JJ.
PLoS One, 8 (7), e42305 (2012)
Díaz A, Díaz-Lobo M, Grados E, Guinovart JJ, Fita I and Ferrer JC.
Iubmb Life, 7 (64), 649-58 (2012)
Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M* and Guinovart JJ*.
EMBO Mol Med, 8 (4), 719-29 (2012)
Rodriguez-Hernandez CJ, Guinovart JJ and Murguia JR.
Febs Lett, 3 (586), 270-6 (2012)
Bultot L, Guigas B, Von Wilamowitz-Moellendorff A, Maisin L, Vertommen D, Hussain N, Beullens M, Guinovart JJ, Foretz M, Viollet B, Sakamoto K, Hue L and Rider MH.
Biochem J, 1 (443), 193-203 (2012)
Díaz A, Martínez-Pons C, Fita I, Ferrer JC and Guinovart JJ.
J Biol Chem, 21 (286), 18505-14 (2011)
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, 11 (3), 667-81 (2011)
Ros S, Zafra D, Valles-Ortega J, García-Rocha M, Forrow S, Domínguez J, Calbó J and Guinovart JJ.
J Biol Chem, 48 (285), 37170-7 (2010)
Pescador N, Villar D, Cifuentes D, Garcia-Rocha M, Ortiz-Barahona A, Vazquez S, Ordoñez A, Cuevas Y, Saez-Morales D, Garcia-Bermejo ML, Landazuri MO, Guinovart J and del Peso L.
PLoS One, 3 (5), e9644 (2010)
Ros S, García-Rocha M, Domínguez J, Ferrer JC and Guinovart JJ.
J Biol Chem, 10 (284), 6370-8 (2009)
Girón MD, Sevillano N, Vargas AM, Domínguez J, Guinovart JJ and Salto R
Diabetologia, 7 (51), 1285-95 (2008)
Solaz-Fuster MC, Gimeno-Alcañiz JV, Ros S, Fernandez-Sanchez ME, Garcia-Fojeda B, Criado Garcia O, Vilchez D, Dominguez J, Garcia-Rocha M, Sanchez-Piris M, Aguado C, Knecht E, Serratosa J, Guinovart JJ, Sanz P and Rodriguez de Córdoba S
Hum Mol Genet, 5 (17), 667-78 (2008)
Cifuentes D, Martínez-Pons C, García-Rocha M, Galina A, Ribas de Pouplana L and Guinovart JJ.
J Biol Chem, 9 (283), 5642-9 (2008)
Vilchez D, Ros S, Cifuentes D, Pujadas Ll, Vallès J, García-Fojeda B, Criado-García O, Fernández-Sánchez E, Medraño MI, Domínguez J, García Rocha M, Soriano E, Rodríguez de Córdoba S and Guinovart JJ
Nat Neurosci, 11 (10), 1407-13 (2007)

* shared senior authorship

Group news & mentions

1 Apr 2014

Joan J. Guinovart, director of the Institute for Research in Biomedicine (IRB Barcelona) has been awarded the prestigious "Creu de Sant Jordi" 2014 (St.

13 Mar 2014

The magazine of the Federation of Spanish Diabetics, DiabetesFEDE, publishes an interview with Joan Guinovart on the latest developments in the field of cell metabolism, in particu

9 Mar 2014

Researchers at IRB, Jordi Duran and Modesto Orozco, have been consulted by the journalist Cristina Sáez for an article on memory for the Magazine

27 Feb 2014

Several media have echoed the studies of Dr.

Upcoming events

29 Oct

Speaker: Dr. James Gordon,
Structural Characterization of macromolecular assemblies, IRB Barcelona, Spain

29 Oct

Speaker: Dr. Maribel Geli,
The endocytic pathway and the actin cytoskeleton, IBMB- CSIC, Barcelona, Spain

31 Oct

Speaker: Dr. Alfonso Martínez Arias,
Dept. of Genetics, University of Cambridge, UK

Funding

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