summary The mass of β secretive insulin cells is a dynamic tissue that adapts to changes in metabolic demand to ensure normoglycaemia. This is done by changing the secretion of insulin and the total mass of β cells. Complete or partial loss of β cells leads to type 1 diabetes and type 2 diabetes respectively. There is still little knowledge of the mechanisms that regulate the mass of β cells and maintain their heterogenated phenotype. Their identification is necessary to understand the development of diabetes and develop treatment strategies. Island grafting is a promising therapeutic approach for type 1 diabetes, but is limited by an early loss of β cells due to cytokin-induced apoptose. In order to improve the survival of β cells during block grafting, the first aim was to find peptides that could block the apoptose induced by FasL and TNF-α. To this end, two phage bookshops were screened to select peptides binding on FAS DD or TNFRl DD. We identified six different peptides. However, none of them was able to protect the cells from FasL-induced apoptose or TNF-α. Second, GLP-1 is a hormone that stimulates insulin secretion, and is involved in β cell proliferation, differentiation, and inhibits apoptose. We assumed that GLP-1 plays a crucial role in controlling the mass and function of β cells. In order to evaluate it, DNA chip analysis was carried out by comparing βTC-Tet cells treated with GLP-1 with untreated cells. 376 regulated genes were identified, including RGS2, CREM, ICERI and DUSP14, significantly increased by GLP-1. We confirmed that GLP-1 increases the expression of these genes, both in transcripts and proteins. In addition, we have shown that GLP-1 induces their expression by activation of the camp/PKA lane, and requires the entry of extracellular calcium. Based on their biological function, we then assumed that these genes could act as negative regulators for GLP-l signalling and thus curb its proliferating effect. To verify our hypothesis, siRNAs against these genes have been developed and their effects on β cell proliferation will be assessed at a later stage. Abstract The Pancreatic β-cell mass is a dynamic tissue which adapts to variations in metabolic demand in order to ensure normoglycemia. This adaptation occurs through a change in both insulin secretion and the total mass of, β-cells. An absolute or relative loss of β-cells leads to type 1 and type 2 diabetes, respected. The mechanisms that regulate the Pancreatic β-cell mass and maintenance of the fully qualified phenotype of the insulin-secting β-cells are only poorly defined. Their identification is required to understand the progression of diabetes, but also to design strategies for the treatment of diabetes. Islet transplantation is a promising thermal approach for type 1 diabetes, but it is still limited by an early Graft loss due to cytokine-induced apoptosis. In order to improve β-cell survival during Islamet transplantation, our first aim was to end novel blockers of FasL- and TNF-α-mediated cell death in the form of peptides. To that end, we SCREENED two display booklets to select FAS DD- or TNFR1 DD-binding peptides. We identify six different small peptides. However, none of these peptides was able to prevent cells from FasL- or TNF-α-mediated apoptosis. Second, GLP-1 is a hormone that has been shown to stimulate insulin secretion and to be involved in β-cell proliferation, discrimination and inhibition of apoptosis. We restricted that GLP-1 plays a crucial role to control mass and function of β-cells. To evaluate this hypothesis, we perform a CDNA microarray analysis with GLP-1-treated βTC-Tet cells compared to untreated cells. We found 376 regulated genes, among these, RGS2, CREM, ICERI and DUSP14, which were maintained by GLP-1. We confirmed that both their mRNA and protein levels were exhausted and repeated after GLP-1 treatment. Moreover, we find that GLP-1 activates their expression maintained through the activation of the camp/PKA signaling pathway, and requests extracellular calcium entry. According to their biological function, we then inhibited that these genes might act as negative regulators of the GLP-1 signaling. In particular, they might brake the effects of GLP-1 on β-cell proliferation. To verify this hypothesis, siRNAs against these genes were developed. The effect of these siRNAs on GLP-1-inducted β-cell proliferation will be evaluated later.