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Research Programmes

Molecular Medicine

Metabolic engineering and diabetes therapy

Joan J. Guinovart

Joan J. Guinovart

Group Leader
Professor (Biochemistry and Molecular Biology Dept. - UB)
Office Tel : +34 93 40 37111

e-mail : guinovartirbbarcelona.org

Background

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.

Research Interests
  • 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.
Research Lines

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.
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
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Institute for Research in Biomedicine (IRB Barcelona)
Parc Científic de Barcelona
C/ Baldiri Reixac 10
08028 Barcelona - Spain
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