Institut de recherche biomédicale
     
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    Equipe : Contrôle du pancréas endocrine

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    Responsable :


                                                                          

    Our global objective is to better understand pancreatic beta cell development, a basis for the development of new therapies of diabetes.

    Our strategy
    is to dissect the role of intercellular signals and environmental factors in the control of pancreatic endocrine cell development in rodent. We develop in parallel innovative tools to translate data from rodent to human pancreas. Finally, we are progressing in the characterization of specific forms of neonatal diabetes in Human.

    We are following a multistep strategy:

    -1- Development of in vitro models that mimic beta cell development from rodent pancreatic progenitors;

    -2- Use such rodent models to screen for signals that modulate beta cell development;

    -3- Development of models that mimic beta cell development from human pancreatic progenitors; use of such human models and data generated in rodent to increase knowledge on human pancreas development;

    -4- Use our expertise on pancreas development and our models to develop human beta cell lines, a tool to study human beta cells.

    -5- Use our knowledge on human pancreas development to better understand specific forms of neonatal diabetes in human.



    Publications 2014


    Scharfmann R, Pechberty S, Hazhouz Y, von Bülow M, Bricout-Neveu E, Grenier-Godard M, Guez F, Rachdi L, Lohmann M, Czernichow P, Ravassard P. A conditionally immortalized human pancreatic beta cell line. J Clin Invest 2014 12:2087-98

    Busiah K, Verkarre V, Cave H, Scharfmann R, Polak M. Human Pancreas Endocrine Cells Populations and ABCC8 Activating Mutations. Horm Res Paediatr 2014 82:59-64

    Rachdi L, Kariyawasam D, Guez F, Aiello V, Arbonés ML, Janel N, Delabar JM, Polak M, Scharfmann R. Dyrk1a haploinsufficiency induces diabetes through decreased pancreatic beta cell mass. Diabetologia 2014 57:960-9

    Publications 2013


    Zertal-Zidani S, Busiah K, Edelman A, Polak M, Scharfmann R. Small-molecule inhibitors of the cystic fibrosis transmembrane conductance regulator increase pancreatic endocrine cell development in rat and mouse. Diabetologia. 2013 56:330-339

    Scharfmann R, Rachdi L, Ravassard P. Concise Review: In Search of Unlimited Sources of Functional Human Pancreatic Beta Cells. Stem Cells Transl Med. 2013 2:61-67

    Fourcade G, Colombo BM, Grégoire S, Baeyens A, Rachdi L, Guez F, Goffin V, Scharfmann R, Salomon BL. Fetal Pancreas Transplants Are Dependent on Prolactin for Their Development and Prevent Type 1 Diabetes in Syngeneic but not Allogeneic Mice. Diabetes. 2013 62:1646-1655

    Denis JA, Gauthier M, Rachdi L, Aubert S, Giraud-Triboult K, Poydenot P, Benchoua A, Champon B, Maury Y, Baldeschi C, Scharfmann R, Piétu G, Peschanski M, Martinat C. mTOR-dependent proliferation defect in human ES-derived neural stem cells affected by Myotonic Dystrophy Type1. J Cell Sci. 2013 126:1763-1772

    Mokhtari D, Al-Amin A, Turpaev K, Li T, Idevall-Hagren O, Li J, Wuttke A, Fred RG, Ravassard P, Scharfmann R, Tengholm A, Welsh N. Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl. Diabetologia. 2013 56:1727-1738

    Bonnefond A, Vaillant E, Philippe J, Skrobek B, Lobbens S, Yengo L, Huyvaert M, Cavé H, Busiah K, Scharfmann R, Polak M, Abdul-Rasoul M, Froguel P, Vaxillaire M. Transcription factor gene MNX1 is a novel cause of permanent neonatal diabetes in a consanguineous family. Diabetes Metab. 2013 39:276-280

    Capito C, Simon MT, Aiello V, Clark A, Aigrain Y, Ravassard P, Scharfmann R. The mouse muscle as an ectopic permissive site for human pancreatic development. Diabetes. 2013 62:3479–3487.

    Busiah K, Drunat S, Vaivre-Douret L, Bonnefond A, Simon A, Flechtner I, Gérard B, Pouvreau N, Elie C, Nimri R, De Vries L, Tubiana Rufi N, Metz C, Bertrand AM, Nivot-Adamiak S, de Kerdanet M, Stuckens C, Jennane F, Sulmont V, Letallec C, Ser N, Désirée C, Pereira S, M Phillip, Scharfmann R, Froguel P, Czernichow P, Vaxillaire M, Polak M, Cavé H. Diabetes Mellitus Phenotype and genotype analysis in a cohort of 175 patients with Neonatal shows frequent association with malformations and neuro-psychological dysfunctions. The Lancet Diabetes & Endocrinology. 2013 1:199-207

    Michau A, Guillemain G, Grosfeld A, Vuillaumier-Barrot S, Grand T, Keck M, L’Hoste S, Chateau D, Serradas P, Teulon J, De Lonlay P, Scharfman R, Brot-Laroche E, Leturque A, Le Gall M. Mutations in SLC2A2 reveal hGLUT2 function in pancreatic ß cell development. J Biol Chem. 2013 288:31080-92