Abstract: The present invention relates to recombinant variants of R-spondin proteins and their use as a medicament, in particular for the treatment of diabetes.

Abstract: The disclosure relates to Rspo 1 proteins and their use as a medicament, in particular for the treatment of diabetes, such as diabete type 1 or 2. The disclosure also relates to methods for inducing the proliferation of pancreatic beta cells in a human subject in need thereof, said method comprising administering an efficient amount of an Rspo 1 protein in said subject. Inventors have surprisingly shown that treatments with recombinant Rspo1 protein induce in vivo proliferation of functional pancreatic beta cells, and improve glucose tolerance and increase glucose-stimulated insulin secretion (GSIS) in mice models of diabete. In addition, they found out that upon near complete beta-cell ablation, the remaining beta-cells could be induced with Rspo 1 protein administration to proliferate and reconstitute a functional beta-cells mass able to maintain euglycemia.

Abstract: The present invention relates to methods and pharmaceutical compositions useful for the treatment of hyperglycemia. Thorough multiple analyses, inventors demonstrated that Gfi1 is expressed in pancreatic acinar cells, starting from the first stages of pancreatic embryonic development. Furthermore, they observed that Gfi1 mRNA levels remain steady throughout embryonic development, while they significantly increase during the first days of life. They challenged conditional mutant mice with high fat diet for 5 months and monitored their weight and glycemia weekly. All the animals displayed a rapid increase in body mass as expected. While control mice rapidly developed a massive hyperglycemia, mutant mice remained normoglycemic throughout the entire experiment. A similar protection from induced diabetes was observed upon treatment with a high dose of Streptozotocin.

Abstract: The present invention relates to methods and pharmaceutical compositions useful for the treatment of hyperglycemia. Thorough multiple analyses, inventors demonstrated that Gfi1 is expressed in pancreatic acinar cells, starting from the first stages of pancreatic embryonic development. Furthermore, they observed that Gfi1 mRNA levels remain steady throughout embryonic development, while they significantly increase during the first days of life. They challenged conditional mutant mice with high fat diet for 5 months and monitored their weight and glycemia weekly. All the animals displayed a rapid increase in body mass as expected. While control mice rapidly developed a massive hyperglycemia, mutant mice remained normoglycemic throughout the entire experiment. A similar protection from induced diabetes was observed upon treatment with a high dose of Streptozotocin.

Abstract: The present invention relates to methods of generating a population of beta cells from a population of alpha cells, by contacting said population of alpha cells with GABA or a GABA receptor agonist, in combination with a monoclonal glucagon neutralizing antibody or other alpha cell mass regulating compounds, for an improved diabetes therapy.

Abstract: The present invention relates to methods and pharmaceutical compositions useful for the treatment of hyperglycemia. Thorough multiple analyses, inventors demonstrated that Gfi1 is expressed in pancreatic acinar cells, starting from the first stages of pancreatic embryonic development. Furthermore, they observed that Gfi1 mRNA levels remain steady throughout embryonic development, while they significantly increase during the first days of life. They challenged conditional mutant mice with high fat diet for 5 months and monitored their weight and glycemia weekly. All the animals displayed a rapid increase in body mass as expected. While control mice rapidly developed a massive hyperglycemia, mutant mice remained normoglycemic throughout the entire experiment. A similar protection from induced diabetes was observed upon treatment with a high dose of Streptozotocin.

Abstract: The present invention relates to methods of generating a population of beta cells from a population of alpha cells, by contacting said population of alpha cells with GABA or a GABA receptor agonist, in combination with a monoclonal glucagon neutralizing antibody or other alpha cell mass regulating compounds, for an improved diabetes therapy.

Abstract: The present invention relates to an in vitro or ex vivo method for producing a population of pancreatic beta-cells, comprising the step of inhibiting the expression or the activity of Arx in a population of pancreatic alpha-cells. The present invention also relates to method for inducing the conversion of pancreatic alpha-cells in pancreatic beta-cells in a patient in need thereof.

Abstract: The present invention relates to an in vitro or ex vivo method for producing a population of pancreatic beta-cells, comprising the step of inhibiting the expression or the activity of Arx in a population of pancreatic alpha-cells. The present invention also relates to method for inducing the conversion of pancreatic alpha-cells in pancreatic beta-cells in a patient in need thereof.

Abstract: The present invention relates to in vitro and in vivo methods for the generation of pancreatic ?-cells, comprising the step of providing at least one pancreatic ?-cell or at least one precursor cell with Pax-4 or a nucleic acid encoding Pax-4. Furthermore, the invention relates to a screening method for the screening of a pancreatic-?-cell phenotype-inducing compound, comprising the step of contacting at least one pancreatic ?-cell or at least one precursor cell with a given compound, and testing whether said compound is capable of inducing a pancreatic-?-cell phenotype.

Abstract: The present invention relates to in vitro and in vivo methods for the generation of pancreatic ?-cells, comprising the step of providing at least one pancreatic ?-cell or at least one precursor cell with Pax-4 or a nucleic acid encoding Pax-4. Furthermore, the invention relates to a screening method for the screening of a pancreatic-?-cell phenotype-inducing compound, comprising the step of contacting at least one pancreatic ?-cell or at least one precursor cell with a given compound, and testing whether said compound is capable of inducing a pancreatic-?-cell phenotype.