Agents for proliferating pancreatic beta-cells of the islets of langerhans, agents for suppressing apoptosis of said cells, and screening of candidate compounds for these agents

• US 20060134063A1
• Filed: 11/21/2005
• Published: 06/22/2006
• Est. Priority Date: 06/02/2000
• Status: Abandoned Application

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Pharmaceutical Company Limited
• Inventors: Okamoto, Hiroshi
• Application Number:
  US11/284,489
• Publication Number:
  US 20060134063A1
• Time in Patent Office: Days
• US Class Current: 424/85.100
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/474 Pancreatic thread protein; Reg protein
• CPC Class Codes: C07K 14/4753 Hepatocyte growth factor; Scatter factor; Tumor cytotoxic factor II
• CPC Class Codes: G01N 2500/20 cell-free systems
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5017 for testing neoplastic activity
• CPC Class Codes: G01N 33/5023 on expression patterns
• CPC Class Codes: G01N 33/507 Pancreatic cells

Abstract

The present invention provides agents for proliferating pancreatic β-cells of Langerhans'"'"' islets, agents for suppressing apoptosis of the cells, and methods of screening for candidate compounds for these agents. The combined use of an inflammatory mediator IL-6 and glucocorticoid remarkably induces the expression of Reg gene in β cells and thus promotes proliferation of β cells. HGF suppresses apoptosis induced by Reg protein and IL-6 and glucocorticoid induce intracellular expression of HGF gene. PARP inhibitors such as nicotinamide and 3-aminobenzamide further enhance the induction of the expression of these genes. Moreover, based on the analysis of the expression induction mechanism using the promoter regions of Reg gene and HGF gene, methods of efficiently screening for candidate compounds for these gene expression inducers have been developed.

Claims

1. A method for proliferating pancreatic β

-cells of Langerhans'"'"' islets with suppressed apoptosis, said method comprising administering a cytokine whose receptor is gp130 and a glucocorticoid to said cells, thereby both hepatocyte growth factor (HGF) and Reg protein is contacted with said β

-cells.

4. The method of claim 1, wherein said cytokine is any one of IL-6, IL-11, LIF, CNTF, OSM or CT-1.

6. The method of claim 1, wherein said glucocorticoid is dexamethasone.

8. The method of claim 1, further comprises administering a poly(ADP-ribose) synthetase/polymerase (PARP) inhibitor.

10. The method of claim 8, wherein said poly(ADP-ribose) synthetase/polymerase (PARP) inhibitor is nicotinamide or 3-aminobenzamide.

2. A method for proliferating pancreatic β

-cells of Langerhans'"'"' islets with suppressed apoptosis, said method comprising administering (i) hepatocyte growth factor (HGF) or a nucleic acid coding for HGF and (ii) Reg protein or a nucleic acid coding for Reg protein to said cells, thereby both HGF and Reg protein is contacted with said α

-cells.

3. The method of claim 2, wherein said method comprises administering hepatocyte growth factor (HGF) and Reg protein to said cells.

5. The method of claim 2, wherein said cytokine is any one of IL-6, IL-11, LIF, CNTF, OSM or CT-1.

7. The method of claim 2, wherein said glucocorticoid is dexamethasone.

9. The method of claim 2, further comprising administering a poly(ADP-ribose) synthetase/polymerase (PARP) inhibitor.

11. The method of claim 9, wherein said poly(ADP-ribose) synthetase/polymerase (PARP) inhibitor is nicotinamide or 3-aminobenzamide.

12. A method of treatment or prophylaxis of diabetes, wherein said method comprises administering a cytokine whose receptor is gp130 and a glucocorticoid to a patient.

13. A method of treatment or prophylaxis of diabetes, wherein said method comprises administering (i) hepatocyte growth factor (HGF) or a nucleic acid coding for HGF and (ii) Reg protein or a nucleic acid coding for Reg protein to a patient.

14. The method of claim 13, wherein said method comprises administering hepatocyte growth factor (HGF) and Reg protein to a patient.