PHYSIOPATHOLOGY OF PANCREATIC BETA CELLS
Department : Physiology - Research axis : Translational biology

Research subject

Pancreatic β-cells are the unique cells of the organism with the capacity to biosynthesize, store and secrete insulin in response to physiological needs. β-cells play a central role in the etiology of Diabetes. Preservation or restoration of a functional β-cell mass is essential. Our objectives, divided into basic research components and clinical investigation, are to examine the cellular and molecular mechanisms controlling function, survival and death of β-cells, to investigate how these go awry in the pathogenesis of diabetes, and how stress and environnement influence β-cell function and survival.

A better understanding of the signaling pathways linked to G-protein coupled receptors (GPCRs) and tyrosine kinase receptors (TKRs) in β-cells is essential to identify new molecular targets to treat Diabetes with the aim to preserve or restore the functional β-cell mass.

The specific aims of our project are :

- To identify the cellular and molecular mechanisms involved in the synergism between signaling pathways engaged by GPCRs (GLP-1 receptors, taken as drug targets for type 2 diabetes), TKRs (Insulin and IGF-1 receptors) and glucose in β-cells.

- To investigate the effects and the mechanisms whereby prolonged exposure to elevated concentration of glucose (chronic hyperglycemia, a key feature of type 2 diabetes), inflammation, or high fat diet adversely affects β cell function and survival.

- To propose and to validate new therapeutic strategies aiming at preserving or restoring a functional β-cell mass in diabetic subjects.

 

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Team

Team leader

Stephane Dalle
DR2, Inserm


  IGF Sud 119

  04 34 35 92 03

 

Magalie Ravier
CRCN, Inserm


  IGF Sud 119

  04 34 35 92 03

 

Staff

Gyslaine Bertrand
CRCN, CNRS


  IGF Sud 119

  04 34 35 92 03

 

Safia Costes
CRCN, Inserm


  IGF Sud 119

  04 34 35 92 03

 

Lou Erhard
Licence pro, Inserm


  IGF Sud 119

  04 34 35 92 03

 

Julia Mathieu
IE CDD, CNRS


  IGF Sud 119

  04 34 35 92 03

 

Joëlle Obeid
Doctorant(e), UM


  IGF Sud 119

  04 34 35 92 03

 

Vincent Venon
Master 1, CNRS


  IGF Sud 119

  04 34 35 92 03

 

Orianne Villard
Doctorant(e), UM


  IGF Sud 119

  04 34 35 92 03

 

Anne Wojtusciszyn
PU-PH, CHU


  IGF Sud 119

  04 34 35 92 03

 


Major publications

  • Leduc M., Richard J., Costes S., Muller D., Varrault A., Compan V., Mathieu J., Tanti JF., Pagès G., Pouyssegur J., Bertrand G., Dalle S., Ravier MA. (2017) ERK1 is dispensable for mouse pancreatic beta cell function but is necessary for glucose-induced full activation of MSK1 and CREB. Diabetologia 60:1999-2010
  • Varin EM., Wojtusciszyn A., Broca C., Muller D., Ravier MA., Ceppo F., Renard E., Tanti JF., Dalle S. (2016) Inhibition of the MAP3 kinase Tpl2 protects rodent and human β-cells from apoptosis and dysfunction induced by cytokines and enhances anti-inflammatory actions of exendin-4. Cell Death Disease 7:e2065
  • Ravier MA., Leduc M., Richard J., Linck N., Varrault A., Pirot N., Roussel M., Bockaert J., Dalle S., Bertrand G. (2014) β-arrestin 2 plays a key role in the modulation of the pancreatic beta cell mass in mice. Diabetologia 57:532-541
  • Ravier MA., Daro D., Prates Roma L., Jonas JC., Cheng-Xue R., Schuit FC., Gilon P. (2011) Mechanisms of control of the free Ca2+ concentration in the endoplasmic reticulum of mouse pancreatic β-cells: interplay with cell metabolism and [Ca2+]c, and role of SERCA2b and SERCA3. Diabetes 60:2533-2445
  • Quoyer J., Longuet C., Broca C., Linck N., Costes S., Varin E., Bockaert J., Bertrand G., Dalle S. (2010) GLP-1 mediates antiapoptotic effect by phosphorylating Bad through a β-arrestin 1-mediated ERK1/2 activation in pancreatic β-cells. J Biol Chem 285:1989-2002
  • Costes S., Vandewalle B., Tourrel-Cuzin C., Broca C., Linck N., Bertrand G., Kerr-Conte J., Portha B., Pattou F., Bockaert J., Dalle S. (2009) Degradation of cAMP-Responsive Element-Binding protein by the ubiquitin-proteasome pathway contributes to glucotoxicity in β-cells and human pancreatic islets. Diabetes 58:1105-1115
  • Broca C., Quoyer J., Costes S., Linck N., Varrault A., Deffayet PM., Bockaert J., Dalle S., Bertrand G. (2009) β-arrestin 1 is required for PAC1 receptor-mediated potentiation of long-lasting ERK1/2 activation by glucose in pancreatic β-cells. J Biol Chem 284:4332-4342

 

 

Events

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