Professor of General Pathology, Dipartimento di Bioogia e Patologia Cellulare e Molecolare, School of Medicine, Università di Napoli Federico II

Research
In 1995, Professor Beguinot established a European Research Network constituted by eight European laboratories to further understanding of type 2 diabetes and its clinical subgroups by extensive phenotype characterization, and to develop more accurate methods of diagnosis and novel therapeutic approaches by the identification of genes and proteins that are related to type 2 diabetes and its complications. In Professor Beguinot’s laboratory, ped was recently identified as a novel type 2 diabetes-related gene that impaired glucose tolerance. It was then found that this abnormality also impairs insulin secretion and insulin action. They now wish to devise agents to manipulate the action of ped protein in the cells. Other ongoing research projects are:

1) Studies of type 2 diabetes subphenotypes associated to defective ped gene expression.
2) Identification of specific functions for each PKC isoform in classical insulin target tissues and in complication target tissues.
3) Genes responsible for beta-cell failure in type 2 diabetes.
4) Genetically modified insulin receptors in major insulin-responsive tissues.
5) The effect of nutritional status on immune response, in particular the effect of leptin on the onset of several autoimmune processes including diabetes in NOD mice, a model of Type 1 diabetes.

Selected publications
Trencia A, Perfetti A, Cassese A, Vigliotta G, Miele C, Oriente F, Santopietro S, Giacco F, Condorelli G, Formisano P, Beguinot F. Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action. Mol Cell Biol 2003;23:4511-21.

Fiory F, Oriente F, Miele C, Romano C, Trencia A, Alberobello AT, Esposito I, Valentino R, Beguinot F, Formisano P. Protein kinase C-zeta and protein kinase B regulate distinct steps of insulin endocytosis and intracellular sorting. J Biol Chem 2004;279:11137-45.

Vigliotta G, Miele C, Santopietro S, Portella G, Perfetti A, Maitan MA, Cassese A, Oriente F, Trencia A, Fiory F, Romano C, Tiveron C, Tatangelo L, Troncone G, Formisano P, Beguinot F. Overexpression of the ped/pea-15 gene causes diabetes by impairing glucose-stimulated insulin secretion in addition to insulin action. Mol Cell Biol 2004;24:5005-15.

Cotugno G, Pollock R, Formisano P, Linher K, Beguinot F, Auricchio A. Pharmacological regulation of the insulin receptor signaling mimics insulin action incells transduced with viral vectors. Hum Gene Ther 2004, in press.

Trencia A, Fiory F, Maitan MA, Vito P, Barbagallo AP, Perfetti A, Miele C, Ungaro P, Oriente F, Cilenti L, Zervos AS, Formisano P, Beguinot F. Omi/HtrA2 promotes cell death by binding and degrading the anti-apoptotic protein ped/pea-15. J Biol Chem 2004 Aug 24 [Epub ahead of print].