Disclosed herein are bacterial proteins that increase pancreatic beta (β) cell number and/or proliferation, methods of increasing β cell number and/or proliferation using such proteins, and methods of treating or inhibiting diabetes in a subject by administering such proteins to the subject. In some embodiments, the protein has at least 80% sequence identity to the amino acid sequence set forth as any one of SEQ ID NOs: 1-7, or fragments thereof. Recombinant vectors including a nucleic acid encoding the protein (such as a nucleic acid encoding a protein with at least 80% sequence identity to any one of SEQ ID NOs: 1-7 or fragments thereof) operably linked to a heterologous promoter are also disclosed. Also disclosed are methods of identifying compounds that increase β cell number and/or proliferation by determining the effect of test compounds on β cell number or proliferation in zebrafish pancreas.

Reg gene receptors are found throughout the body, including in the neurons of the brain and spinal cord, liver and heart. Reg proteins are expressed during fetal development for organogenesis and then only upregulated in times of organ injury, such as in the setting of stroke, myocardial infarction or spinal cord injury. Upregulation of Reg proteins following organ injury is a protective mechanism against organ failure and has been shown to result in the formation of new neurons, cardiac myocytes, hepatocytes and in other organs expressing the Reg receptor. Described are the compositions of bioactive Reg peptides, as well as optimization of these peptides (to increase plasma half-life), peptidomimetics, stimulatory antibodies and small molecules that interact with the Reg receptor that are capable of initiating formation of new cells after organ injury.

Methods are provided for identifying an agent that directly modulates a Bcl-2-associated x-protein (BAX) by promoting or disrupting dimerization of the BAX. Agents that directly modulate BAX by affecting dimerization are also provided.

Methods of identifying compounds that increase cell number and/or proliferation by determining the effect of compounds on cell number or proliferation in zebrafish pancreas are provided.

Peptides that are bioactive regions and optimized bioactive regions of the human and mammalian Reg gene proteins and that are capable of generation of tissues such as brain, spinal cord, heart, liver, and kidney are described. In particular, 7-15-amino acid Reg peptides and optimized Reg peptides are disclosed which are capable of in vivo and ex vivo transformation of progenitor cells, progenitor tissue and stem cells into specialized cells and tissues, including functioning brain and spinal cord neurons, cardiac myocytes, liver hepatocytes and renal nephrons. Methods of in vivo and ex vivo transformation of progenitor cells into differentiated cells and tissues are also described.

Methods are provided for identifying an agent that directly modulates a Bcl-2-associated x-protein (BAX) by promoting or disrupting dimerization of the BAX. Agents that directly modulate BAX by affecting dimerization are also provided.

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.

Embodiments of the present invention provide for novel therapies, pharmaceutical compositions and methods for insulin independence utilizing a new optimized hamster Reg3 gamma peptide, which is new to the art and has not previously been considered for development in the 30 year history since its discovery. Methods, pharmaceutical compositions and therapies novel to the prior art are utilized in this invention to render patients with recent onset and existing type 1 diabetes insulin independent by an optimized hamster Reg3 gamma peptide and an immune tolerance agent for type 1 patients to become insulin independent and used alone without an immune tolerance agent for type 2 diabetes. While not wishing to be bound by theory, optimized Reg3 gamma peptides increases beta cell generation by its demonstrated properties shown within of transforming ductal pancreatic cells into new islets.