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.
López-Soldado I, Zafra D, Duran J, Adrover A, Calbó J and Guinovart JJ.
Diabetes, 64 (3), 796-807 (2015)
Zeqiraj E, Tang X, Hunter RW, García-Rocha M, Judd A, Deak M, von Wilamowitz-Moellendorff A, Kurinov I, Guinovart JJ, Tyers M, Sakamoto K and Sicheri F.
P Natl Acad Sci Usa, 111 (28), E2831-40 (2014)
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)
Rodriguez-Hernandez CJ, Llorens-Agost M, Calbó J, Murguia JR and Guinovart JJ.
Febs Lett, 587 (10), 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, 114 (7), 1653-64 (2013)
Duran J, Saez I, Gruart A, Guinovart JJ and Delgado-García JM.
J Cerebr Blood F Met, 33 (4), 550-6 (2013)
Nocito L, Zafra D, Calbó J, Domínguez J and Guinovart JJ.
PLoS One, 7 (8), e42305 (2012)
Díaz A, Díaz-Lobo M, Grados E, Guinovart JJ, Fita I and Ferrer JC.
Iubmb Life, 64 (7), 649-58 (2012)
Duran J, Tevy MF, Garcia-Rocha M, Calbó J, Milán M* and Guinovart JJ*.
EMBO Mol Med, 4 (8), 719-29 (2012)
Rodriguez-Hernandez CJ, Guinovart JJ and Murguia JR.
Febs Lett, 586 (3), 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, 443 (1), 193-203 (2012)
Díaz A, Martínez-Pons C, Fita I, Ferrer JC and Guinovart JJ.
J Biol Chem, 286 (21), 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, 3 (11), 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, 285 (48), 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, 5 (3), e9644 (2010)
Ros S, García-Rocha M, Domínguez J, Ferrer JC and Guinovart JJ.
J Biol Chem, 284 (10), 6370-8 (2009)
Girón MD, Sevillano N, Vargas AM, Domínguez J, Guinovart JJ and Salto R
Diabetologia, 51 (7), 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, 17 (5), 667-78 (2008)
Cifuentes D, Martínez-Pons C, García-Rocha M, Galina A, Ribas de Pouplana L and Guinovart JJ.
J Biol Chem, 283 (9), 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, 10 (11), 1407-13 (2007)

* 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

Group news & mentions

15 Apr 2015

“Diario Médico” has published an article coinciding with International Pompe Day about the campaign “Investigar salva vidas” (Research saves lives), launched by the “Asociación Española de Enfermos

13 Apr 2015

April 15 is International Pompe Day, a rare condition that affects the muscular development of the body, causing death in infants under one year of age and severe muscle weakness in children and ad

9 Apr 2015

April 15 is International Pompe Day.

14 Nov 2014

The newspaper El Correo, edited in Vizcaya, publishes a whole-page article on the link between the brain and the liver with respect to appetite control.

Upcoming Programme Events

22 Apr

Speaker: Ramesh Yelagandula - Gregor Mendel Institute (GMI), Vienna, Austria 

22 Apr

Speaker: Prof. Boris Turk, PhD

Head of Dept. Biochem. & Mol. & Struct. Biol.

J.Stefan Institute

Ljubljana- Slovenia

 

22 Apr

Speaker: César González, IBMB-CSIC

 

24 Apr

Speaker: Fátima Bosch, PhD

Center of Animal Biotechnology and Gene Therapy.

Universitat Autònoma de Barcelona, Bellaterra - Spain