Abstract: Novel INGAP peptides for prevention or treatment of diabetes are provided herein, as well as compositions and methods of use thereof. In particular, a 19 amino acid peptide of INGAP which possesses ?-cell neogenesis and insulin potentiating activities and is sufficiently stable for in vivo use is described.

Abstract: Pancreatic acinar cells contribute to ?-cell neogenesis. Hamsters administered pentadecapeptide of INGAP protein demonstrated a 2-fold increase in the number of extra-islet acinar-associated ?-cell clusters resulting in a 2.8-fold increase in the overall extra-islet ? cell mass as compared to controls. In mammals acinar-to-?-cell differentiation provides an alternate pathway to ?-cell neogenesis; INGAP peptide plays a significant role in this process.

Abstract: The present invention comprises dosing regimens and formulations of islet cell neogenesis associated protein (INGAP) and INGAP Peptide. The formulation disclosed herein is shown have acceptable stability as a pharmaceutical composition. Further, the formulation is able to regenerate functional islets.

Abstract: A method of polishing a substrate includes polishing a substrate with a generally linear polishing sheet, polishing the substrate with polishing pad composed of a napped poromeric material, and conditioning the polishing pad.

Abstract: A chemical mechanical polishing apparatus has a movable platen, a drive mechanism and a chucking mechanism. The drive mechanism is attached to the platen, is configured to support a generally linear polishing sheet with a portion of the polishing sheet extending over the platen, and is configured to incrementally advance the polishing sheet in a linear direction relative to the platen. The chucking mechanism is configured to intermittently secure the portion of the polishing sheet to the platen.

Abstract: The present invention relates to an in vitro method for screening agents inducing islet cell neogenesis or duct-to-islet cell transdifferentiation, which comprises the steps of: a) expanding in vitro cells of a duct-like structure obtained by inducing cystic formation in cells in or associated with post-natal islets of Langerhans; b) treating said expanded cells of said duct-like structure with an agent screened; and c) determining potency of said agent of inducing islet cell differentiation of said duct-like structure in becoming insulin-producing cells.

Abstract: The present invention relates to a method to stimulate reversal of a diabetic state in a patient; a method to prevent autoimmune destruction of new insulin-producing cells (pancreatic beta-cells) in a patient; a method to promote survival of the newly regenerated insulin-producing cells (pancreatic beta-cells); and an in vivo method for the induction of islet cell neogenesis and new islet formation and the prevention of autoimmune destruction of said new cells.

Abstract: The present invention provides mammalian pancreatic progenitor cells (“small cells”) and methods for their isolation and propagation. The pancreatic small cells are derived from adult pancreatic tissue and are characterised by their small size. The small cells are quiescent or undergo a very slow cell cycle when maintained in cell culture. Small cells secrete synaptophysin and islet hormones and are predominantly found in small, growing islets as small clusters. The present invention further provides for the use of the pancreatic small cells in transplantation and the treatment of diabetes mellitus, and for the genetic engineering of the small cells in order to produce recombinant proteins in vivo.

Abstract: The present invention relates to a medium for preparing dedifferentiated cells derived from post-natal islets of Langerhans. The medium comprises in a physiologically acceptable culture medium an effective amount of a solid matrix environment for a three-dimensional culture, a soluble matrix protein, and a first and a second factor for developing, maintaining and expanding the dedifferentiated cells. Such a medium may be used in an in vitro method for islet cell expansion. The present invention also relates to a medium for inducing islet neogenesis from duct-like structure, which comprises in a physiologically acceptable culture medium an effective amount of at least one islet neogenesis inducer compound.

Abstract: The present invention relates to a neuritogenic compound for neurite outgrowth, which comprises the amino acid sequence: Gly Leu His Asp Pro Ser His Gly Thr Leu Pro Asn Gly Ser Gly (SEQ ID NO:3), functional derivatives and/or fragments thereof and functional peptidometics thereof. There is also provided a method for repair and/or regeneration of peripheral nervous system in a patient.

Abstract: The present invention comprises dosing regimens and formulations of islet cell neogenesis associated protein (INGAP) and INGAP Peptide. The formulation disclosed herein is shown have acceptable stability as a pharmaceutical composition. Further, the formulation is able to regenerate functional islets.

Abstract: The present invention relates to a medium for preparing dedifferentiated cells derived from post-natal islets of Langerhans. The medium comprises in a physiologically acceptable culture medium an effective amount of a solid matrix environment for a three-dimensional culture, a soluble matrix protein, and a first and a second factor for developing, maintaining and expanding the dedifferentiated cells. Such a medium may be used in an in vitro method for islet cell expansion.

Abstract: The present invention relates to a medium for preparing dedifferentiated cells derived from post-natal islets of Langerhans. The medium comprises in a physiologically acceptable culture medium an effective amount of a solid matrix environment for a three-dimensional culture, a soluble matrix protein, and a first and a second factor for developing, maintaining and expanding the dedifferentiated cells. Such a medium may be used in an in vitro method for islet cell expansion.

Abstract: Induction of &bgr;-cell neogenesis has been associated with ductal epithelium, however ˜80% of the pancreas is composed of acinar cells. Surprisingly, pancreatic acinar cells contribute to &bgr;-cell neogenesis. Partial duct obstruction (PDO) of the pancreas is a known inducer of &bgr;-cell neogenesis leading to expansion of &bgr;-cell mass, and the effect appears to be mediated by INGAP, an acinar cell protein originally identified in the regenerating hamster pancreas. We examined the effects of PDO on the incorporation of tritiated thymidine by acinar and &bgr;-cells of the pancreas in female Syrian hamsters. A single dose of tritiated thymidine was administered to all animals 2 weeks after PDO. Animals were then sacrificed at 1 hr, or at 6 weeks post-injection. Tritiated thymidine incorporation into acinar cells was highest at 2 weeks after PDO and declined at 8 weeks after PDO. Incorporation of tritiated thymidine into &bgr;-cells was inversely related to that observed in acinar cells.

Abstract: The present invention relates to an in vitro method for islet cell expansion, which comprises the steps of: a) preparing dedifferentiated cells derived from cells in or associated with post-natal islets of Langerhans; b) expanding the dedifferentiated cells; and c) inducing islet cell differentiation the expanded cells of step b) to become insulin-producing cells.

Abstract: The present invention relates to an in vitro method for islet cell expansion, which comprises the steps of: a) preparing dedifferentiated cells derived from cells in or associated with post-natal islets of Langerhans; b) expanding the dedifferentiated cells; and c) inducing islet cell differentiation the expanded cells of step b) to become insulin-producing cells.

Abstract: A device for cell implantation has a housing containing a matrix which isolates the cells in the housing; the housing has a window which comprises a membrane which permits passage of nutrients for the cells into the matrix from a location externally of the housing; the housing has an injection port permitting injection of cells into the matrix in the housing. The device may be employed, for example, to facilitate islet implantation in the treatment of diabetes mellitus.

Abstract: The present invention relates to a medium for promoting the survival of islet cells, which comprises one or more growth factors in combination with FK506 in amounts having an anti-apoptotic effect on islet cells in a physiologically acceptable culture medium.

Abstract: Cellophane wrapping (CW) of hamster pancreas induces proliferation of duct epithelial cells followed by endocrine cell differentiation and islet neogenesis. Using the mRNA differential display technique a cDNA clone expressed in cellophane wrapped but not in control pancreata was identified. Using this cDNA as a probe, a cDNA library was screened and a gene not previously described was identified and named INGAP.

Abstract: Cellophane wrapping (CW) of hamster pancreas induces proliferation of duct epithelial cells followed by endocrine cell differentiation and islet neogenesis. Using the mRNA differential display technique a cDNA clone expressed in cellophane wrapped but not in control pancreata was identified. Using this cDNA as a probe, a cDNA library was screened and a gene not previously described was identified and named INGAP.