JP4755133B2 - GLP−1またはExendin−4による、非インスリン産生細胞のインスリン産生細胞への分化、およびその使用 - Google Patents
GLP−1またはExendin−4による、非インスリン産生細胞のインスリン産生細胞への分化、およびその使用 Download PDFInfo
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- JP4755133B2 JP4755133B2 JP2007114374A JP2007114374A JP4755133B2 JP 4755133 B2 JP4755133 B2 JP 4755133B2 JP 2007114374 A JP2007114374 A JP 2007114374A JP 2007114374 A JP2007114374 A JP 2007114374A JP 4755133 B2 JP4755133 B2 JP 4755133B2
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- C12N2501/30—Hormones
- C12N2501/335—Glucagon; Glucagon-like peptide [GLP]; Exendin
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Description
Teitelman. Induction of beta‐cell neogenesis by islet injury. Diabetes Metabolism Rev. 12 : 91‐102,1996 Physician’s Guide to Insulin Dependent[Type I]Diabetes Mellitus:Diagnosis and Treatment,American Diabetes Association,1988 UK Prospective Study Group,1995 Bressler, R. and Johnson, G. G. 1997. Pharmacological regulation of blood glucose levels in non‐insulin dependent diabetes. Arch. Int. Med. 157 : 836‐848 Ghazzi et al. 1997. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes. 46 : 433‐439. Care. 15 : 270‐276 Gutniak et al. 1992. Antidiabetogenic effect of glucagon‐like peptide‐1 (7‐36) amide in normal subjects and patients with diabetes mellitus. N . Engl. J. Med. 326 : 1316‐1322 Nauck et al. 1993. preserved incretin activity of Glucagon‐like peptide 1 (7‐36) amide but not of synthetic human gastric inhibitory polypeptide in patients with Type‐2 diabetes mellitus. J. Clin. Invest. 91 : 301‐307 Ochs et al. 1983. Intracellular free calcium concentrations in isolated pancreatic acini : effects of secretagogues. Biochem. Biophys. Res. Commun. 117 : 122‐128 Elahi, et al. 1994. The insulinotropic actions of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (737) in normal and diabetic subjects. Regulatory Peptides. 51 : 63‐74 Wills et al. 1996. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal : effects of exogenous glucagon‐like peptide‐1‐ (7‐36) amide in Type 2 (non‐insulin‐dependent) diabetic patients, J. Clin. Endocrinol. Metab. 81 : 327‐332 Nathan et al. 1992. Insulinotropic action of glucagonlike peptide‐l‐ (7‐37) in diabetic and nondiabetic subjects. Diabetes Care. 15 : 270‐276 De Ore et al. 1997. The effects of GLP‐1 on insulin release in young and old rats in the fasting state and during an intravenous glucose tolerance test. J. Geront. 52 : B245‐249 Wang et al. 1995. Glucagon‐like peptide‐1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046‐38 cells. Endocrinology. 136 : 4910‐4917 Wang et al. 1996. GIP regulates glucose transporters, hexokinases, and glucose‐induced insulin secretion in RIN 1046‐38 cells. Moll. Cell. Endo. 116 : 81‐87 Thorens. 1992. Expression cloning of the pancreatic beta cell receptor for the gluco‐incretin hormone glucagon‐like peptide 1. Proc. Natl. Acad. Sci. USA 89 : 8641‐8645 Orskov. 1992. Glucagon‐like peptide‐1, a new hormone of the entero‐insular axis. Diabetologia. 35 : 701‐711 Drucker et al. 1987. Glucagon ‐like Peptide 1 stimulates insulin gene expression and increases cyclic AMP in a rat islet cell line Proc. Natl. Acad. Sci. USA. 84 : 3434‐3438 Fehmann and Habener. 1992. Insulinotropic hormone glucagon‐like peptide‐1 (7‐37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma BTC‐1 cells. Endocrinology 130 :159‐166 Montrose‐Rafizadeh et al. 1994. Incretin hormones regulate glucose‐dependent insulin secretion in RIN 1046‐38 cells : mechanism of action. Endocrinology. 135 : 589‐594 Fehmann et al. 1995. Cell and Molecular Biology of the Incretin Hormones Glucagon‐Like Peptide‐I and Glucose‐Dependent Insulin Releasing Polypeptide. Endocrine Rev. 16 : 390‐410 Widmann et al. 1996. Desensitization and phosphorylation of the glucagon‐Iike peptide‐1 (GLP‐1) receptor by GLP‐1 and4‐phorbol 12‐Myristate 13‐acetate. Mol. Endocrinol. 10 : 62‐75 Valverde and Villanueva‐Penacarrillo. 1996. In vitro insulinomimetic effects of GLP‐1 in liver, muscle and fat. Acta Physiologica Scandinavica 157 : 359‐360 Goke et al. 1993. Exendin‐4 is a potent agonist and truncated exendin‐ (9‐39) ‐amide an antagonist at the GLP‐l‐ (7‐36) ‐amide receptor of insulin‐secreting ss‐cells. J.Biol. Chem. 268; 19650‐19655 Chen and Drucker. 1997. Tissue‐specific expression of unique mRNAs that encode pro‐glucagon‐derived peptides or exendin‐4 in the lizard. J. Biol. Chem. 272 : 4108‐4115 Thorens et al. 1993. Cloning and functional expression of the GLP‐1 receptor : Demonstration that exendin‐4 is an agonist and exendin‐3 (9‐39) is an antagonist of the receptor. Diabetes. 42 : 1678‐1672 Ritzel et al. 1995. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP‐1 [7‐36 amide] after subcutaneous injection in healthy volunteers. Dose‐response‐relationships. Diabetologia. 38 :720‐725
REFERENCES
1. Arver et al. 1991. Different aetiologies of type 2 (non‐insulin‐dependent) diabetes mellitus in obese and non‐obese subjects. Diabetologia. 34 : 483‐487.
2. Bradford. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein‐dye binding. Annal. Biochem. 72 : 248‐254.
3. Bressler, R. and Johnson, G. G. 1997. Pharmacological regulation of blood glucose levels in non‐insulin dependent diabetes. Arch. Int. Med. 157 : 836‐848.
4. Busik et al. 1997. Glucose‐Specific Regulation of Aldose Reductase in Capan‐1 Human Pancreatic Dcust Cells In Vitro. J. Clin. Invest. 100 : 1685‐1692.
5. Ceska et al. 1969. A new and rapid method for the clinical determination of alpha‐amylase activities in human serum and urine. Clin. Chim. Acta 26 : 437‐444.
6. Chen and Drucker. 1997. Tissue‐specific expression of unique mRNAs that encode pro‐glucagon‐derived peptides or exendin‐4 in the lizard. J. Biol. Chem. 272 : 4108‐4115.
7. bChigwin et al. 1979. Isolation of biologically active ribonucleic acid from sources enriched in ridonuclease. Biochemistry. 18 : 5294‐5299.
8. Chomczynski and Sacchi. 1987. Single‐step method of RNA isolation by acid guanidinium thiocyanate‐phenol‐chloroform extraction. Analyt. Biochem. 162 : 156‐159.
9. Christophe. 1994. Pancreatic tumoral cell line AR42J : an amphicrine model. Am. J. Physiol. 266 : G963‐971.
10. De Ore et al. 1997. The effects of GLP‐1 on insulin release in young and old rats in the fasting state and during an intravenous glucose tolerance test. J. Geront. 52 : B245‐249.
11. Drucker et al. 1987. Glucagon ‐like Peptide 1 stimulates insulin gene expression and increases cyclic AMP in a rat islet cell line Proc. Natl. Acad. Sci. USA. 84 : 3434‐3438.
12. Egan et al. 1994. Glucagon‐like peptide‐1 (7‐36) amide (GLP‐1) enhances insulin‐stimulated glucose metabolism in 3T3‐L1 adipocytes : one of several potential extrapancreatic sites ofGLP‐1 action. Endocrinology 135 : 2070‐2075.
13. Egan et al. 1991. Glucose stimulated insulin release by individual beta cells : potentiation by glyburide. J. Exp. Med. Biol. 196 : 203‐210.
14. Elahi, et al. 1994. The insulinotropic actions of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (737) in normal and diabetic subjects. Regulatory Peptides. 51 : 63‐74.
15. Elahi, et al. 1985. The effect of age and glucose concentration on insulin secretion by the isolated perfused pancreas. Endocrinology 116 : 11‐16.
16. Fehmann and Habener. 1992. Insul
of proinsulin gene expression and proinsulin biosynthesis in insulinoma BTC‐1 cells. Endocrinology 130 :
159‐166.
17. Fehmann et al. 1995. Cell and Molecular Biology of the Incretin Hormones Glucagon‐Like Peptide‐I and Glucose‐Dependent Insulin Releasing Polypeptide. Endocrine Rev. 16 : 390‐410.
18. Ghazzi et al. 1997. Cardiac and glycemic benefits of troglitazone treatment in NIDDM. Diabetes. 46 : 433−439. Care. 15 : 270‐276.
19. Glisin et al. 1974. Ribonucleic acid isolated by cesium chloride centrifugation. Biochemistry. 13 : 2633‐2637.
20. Goke et al. 1993. Exendin‐4 is a potent agonist and truncated exendin‐ (9‐39) ‐amide an antagonist at the GLP‐l‐ (7‐36) ‐amide receptor of insulin‐secreting ss‐cells. J.Biol. Chem. 268; 19650‐19655.
21. Goldfine et al. 1997. The Endocrine Secretion of Human Insulin and Growth Hormone by Exocrine Glands of the Gastrointestinal Tract. Nature Biotechnology 15 : 1378‐1382.
22. Gromada et al. 1998. Glucagon‐Like Peptide 1 (7‐36) Amide Stimulates Exocytosis in Human Pancreatic p‐Cells by Both Proximal and Distal Regulatory Steps in Stimulus‐Secretion Coupling. Diabetes 47 : 57‐65.
23. Gutniak et al. 1992. Antidiabetogenic effect of glucagon‐like peptide‐1 (7‐36) amide in normal subjects and patients with diabetes mellitus. N . Engl. J. Med. 326 : 1316‐1322.
24. Guz et al. 1995. Expression ofmurine STF‐1, a putative insulin gene transcription factor, in 13 cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny. Development 121 : 11‐18.
25. Hawes et al. 1995. Distinct pathways of Gj‐and Gq‐mediated mitogen ‐ activated protein kinase activation. J. Biol. Chem. 270 : 17148‐17153.
26. Holz et al. 1995. Activation of a cAMP‐regulated Ca2+ ‐signaling pathway in pancreatic beta‐cells by the insulinotropic hormone glucagon‐like‐peptide‐l. J. Biol. Chem. 270: 17749‐17757.
27. Hosokawa et al. 1996. Mechanism of impaired glucose‐potentiated insulin secretion in diabetic 90% pancreatectomy rats. Study using glucagonlike peptide‐1 (7‐37). J. Clin. Invest. 97 : 180‐186.
28. Hsu et al. 1981. Use of avidin‐biotin‐peroxidase complex (ABC) in immunoperoxidase techniques : A comparison between (ABC) and unlabeled antibody (PAP) procedures. J Histochem. Cytochem. 29:
577‐580.
29. Janczewski and Lakatta. 1993. Buffering of calcium influx by sarcoplasmic reticulum during the action potential in guinea‐pig ventricular myocytes. J. Physiol. 471 : 343‐363.
30. Kimura et al. 1996. High concentrations of cholecystokinin octapeptide suppress protein kinase C activity in guinea pig pancreatic acini. Peptides 17 : 917‐925.
31. Konnerth et al. 1986. Nonsynaptic epileptogenesis in the mammalian
hippocampus in vitro. I. Development of seizurelike activity in low
extracellular calcium. J. Neurophysiol. 56 : 409‐423.
32. Logsdon et al. 1987. Mechanism of glucocorticoid‐induced increase in pancreatic amylase gene transcription. J. Biol. Chem. 262 : 15765‐15769.
33. Lutz et al. 1993. A role for cholecystokinin‐stimulated protein tyrosine phosphorylation in regulated secretion by the pancreatic acinar cell. J. Biol. Chem. 268 : 11119‐11124.
34. Malhotra et al. 1992. Exendin‐4, a new peptide from heloderma suspectum venom, potentiates cholecystokinin‐induced amylase release from rat pancreatic acini. Regul. Pept. 41 : 149‐156.
35. Mashima et al. 1996. Betacellulin and activin A coordinately convert amylase‐secreting AR42J cells into insulin‐secreting cells. J. Clin. Invest. 97 : 1647‐1654.
36. Mashima et al. 1996, Formation of Insulin‐Producing Cells from Pancreatic Acinar AR42J Cells by Hepatocyte Growth Factor. Endocrinology 137 : 3969‐3976.
37. Matschinsky. 1990. Glucokinase as glucose sensor and metabolic signal generator in pancreatic 6‐celles. Diabetes. 39 : 647‐652.
38. Montrose‐Rafizadeh et al. 1997. High potency antagonists of the pancreatic glucagon‐like peptide‐1 receptor. J. Biol. Chem. 272 :21201‐21206.
39. Montrose‐Rafizadeh et al. 1994. Incretin hormones regulate glucose‐dependent insulin secretion in RIN 1046‐38 cells : mechanism of action. Endocrinology. 135 : 589‐594.
40. Montrose‐Rafizadeh et al. 1997. Evidence of direct coupling of pancreatic GLP‐1 receptor to different G‐protein alpha subunits. Diabetes 46 : 0724a (Abstr.)
41. Montrose‐Rafizadeh et al. 1997. Novel signal transduction and peptide specificity of glucagon‐like peptide receptor in 3T3‐L1 adipocytes. J. Cell. Physiol. 172 : 275‐280.
42. Muallem et al. 1988. Agonist‐sensitive calcium pool in the pancreatic acinar cell. I. Permeability properties. Am. J. Physiol. 255 : G221‐228.
43. Mueckler. 1990. Family of glucose‐transporter genes. Implications for glucose homeostasis and diabetes. Diabetes. 39 : 6‐11.
44. Nathan et al. 1992. Insulinotropic action of glucagonlike peptide‐l‐ (7‐37) in diabetic and nondiabetic subjects. Diabetes Care. 15 : 270‐276.
45. Nauck et al. 1993. preserved incretin activity of Glucagon‐like peptide 1 (7‐36) amide but not of synthetic human gastric inhibitory polypeptide in patients with Type‐2 diabetes mellitus. J. Clin. Invest. 91 : 301‐307.
46. Nauck et al. 1993. normalization of fasting hyperglycemia by exogenous glucagon‐like peptide 1 (7‐36) amide in Type 2 (non‐insulin‐dependent) diabetic patients. Diabetologia. 36 : 741‐744.
47. Nishizuka. 1984. The role of protein kinase C in cell surface signal transduction and tumor promotion. Nature 308: 693‐698.
48. Ochs et al. 1983. Intracellular free calcium concentrations in isolated pancreatic acini : effects of secretagogues. Biochem. Biophys. Res. Commun. 117 : 122‐128.
49. Offermanns et al. 1993. Stimulation of tyrosine phosphorylation and mitogen‐activated‐protein (MAP) kinase activity in human SH‐SY5Y neuroblastoma cells by carbachol. Biochem. J. 294 : 545‐550.
50. Orskov. 1992. Glucagon‐like peptide‐1, a new hormone of the entero‐insular axis. Diabetologia. 35 : 701‐711.
51. Perfetti et al. 1995. Age‐dependent reduction in insulin secretion and insulin mRNA in isolated islets from rats. Am. J. Physiol. 269 : E983‐990.
52. Physician’s Guide to Insulin Dependent Type IJ Diabetes Mellitus : Diagnosis and Treatment. American Diabetes Association, 1988.
53. Rall et al. 1973. Early differentiation of glucagon‐producing cells in embryonic pancreas ; a possible developmental role for glucagon. Proc.
Nat. Acad. S ci. USA 70 : 3478‐3482.
54. Ritzel et al. 1995. Pharmacokinetic, insulinotropic, and glucagonostatic properties of GLP‐1 [7‐36 amide] after subcutaneous injection in healthy volunteers. Dose‐response‐relationships. Diabetologia. 38 :
720‐725.
55. Rivard et al. 1995. Novel model of integration of signaling pathways in rat pancreatic acinar cells. Am. J. Physiol. 269 : G352‐G362.
56. Saiki et al. 1988. Primer‐directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science 239 : 487‐491.
57. Schaffert et al. 1997. Modification of Blood Group A Expression in Human Pancreatic Tumor Cell Lines by Inhibitors of N‐Glycan Processing. Internat ’I J Pancreatology 21: 21 ‐29.
58. Schnefel et al. 1990. Cholecystokinin activates Gjl‐, Gj2‐, Gj3‐and several Gs‐proteins in rat pancreatic acinar cells. Biochem. J. 269 :
483‐488.
59. Siddhanti et al. 1995. Forskolin inhibits protein kinase C‐induced mitogen‐activated protein kinase activity in MC3T3‐E1 osteoblasts. Endocrinology. 136 : 4834‐4841.
60. Spurgeon et al. 1990. Simultaneous measurement of Cas+, contraction, and potential in cardiac myocytes. Am. J. Physiol. 258 : H574‐H586.
61. Steiner et al. 1972. Radioimmunoassay for cyclic nucleotides II adenosine 3’, 5’‐monophosphate and guanosine 3’, 5’‐monophosphate in mammalian tissues and body fluids. J. Biol. Chem. 247 : 1114‐1120.
62. Teitelman. Induction of beta‐cell neogenesis by islet injury. Diabetes Metabolism Rev. 12 : 91‐102,1996.
63. Thorens. 1992. Expression cloning of the pancreatic beta cell receptor for the gluco‐incretin hormone glucagon‐like peptide 1. Proc. Natl. Acad. Sci. USA 89 : 8641‐8645.
64. Thorens et al. 1993. Cloning and functional expression of the GLP‐1 receptor : Demonstration that exendin‐4 is an agonist and exendin‐3 (9‐39) is an antagonist of the receptor. Diabetes. 42 : 1678‐1672.
65. Thorens and Waeber. 1993. Glucagon‐like peptide‐1 and the control of insulin secretion in the normal state and in NIDDM. Diabetes. 42 : 1219‐1225.
66. UK Prospective Study Group. 1995. UK Prospective Diabetes Study 16 : Overview of 6 years’therapy of Type 2 diabetes : A progressive disease. Diabetes. 44 : 1249‐1258.
67. Vajanaphanich et al. 1995. Cross‐talk between calcium and cAMP‐dependent intracellular signaling pathways. J. Clin. Invest. 96 :386‐393.
68. Valverde and Villanueva‐Penacarrillo. 1996. In vitro insulinomimetic effects of GLP‐1 in liver, muscle and fat. Acta Physiologica Scandinavica 157 : 359‐360.
69. von Weizsacker et al. 1992. Diversity among the beta subunits of heterotrimeric GTP‐binding proteins ; Characterization of a novel beta‐subunit cDNA. Biochem. Biophys. Res. Commun. 183 : 350‐356.
70. Wang et al. 1997. Glucagon‐like peptides‐1 can reverse the age related decline in glucose tolerance in rats. J. Clin. Invest. 99 : 2883‐2889.
71. Wang et al. 1995. Glucagon‐like peptide‐1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046‐38 cells. Endocrinology. 136 : 4910‐4917.
72. Wang et al. 1996. GIP regulates glucose transporters, hexokinases, and glucose‐induced insulin secretion in RIN 1046‐38 cells. Moll. Cell. Endo. 116 : 81‐87.
73. Wang et al. 1995. Glucagon‐like peptide‐1 is a physiological incretin in rat. J. Clin. Invest. 95 : 417‐421.
74. Wang et al. 1988. Effects of aging on insulin synthesis and secretion. Differential effects on proinsulin messenger mRNA levels, proinsulin biosynthesis, and secretion of newly made and preformed insulin in the rat. J. Clin. Invest. 81 : 176‐184.
75. Wang and Rowe. 1988. Age‐related impairment in the short term regulation of insulin biosynthesis by glucose in rat pancreatic islets. Endocrinology 123 : 1008‐1013.
76. Widmann et al. 1996. Desensitization and phosphorylation of the glucagon‐Iike peptide‐1 (GLP‐1) receptor by GLP‐1 and4‐phorbol 12‐Myristate 13‐acetate. Mol. Endocrinol. 10 : 62‐75.
77. Wills et al. 1996. Gastric emptying, glucose responses, and insulin secretion after a liquid test meal : effects of exogenous glucagon‐like peptide‐1‐ (7‐36) amide in Type 2 (non‐insulin‐dependent) diabetic patients, J. Clin. Endocrinol. Metab. 81 : 327‐332.
78. Yada et al. Glucagon‐like peptide‐1‐ (7‐3 6) amide and a rise in cyclic adenosine 3’, 5’‐monophosphate increase cytosolic free Ca2+ in rat pancreatic B‐cells by enhancing Ca2+ channel activity. Endocrinology 133 : 1685‐1692.
79. Zamponi et al. 1997. Crosstalk between G proteins and protein kinase C mediated by the calcium channel alpha 1 subunit. Nature. 385 : 442‐446.
80. Scharp et al. 1991. Transplant. 51 : 76.
81. Warnock et al. 1991. Diabetologia 34 : 55.
Claims (20)
- GLP−1レセプターを有する非インスリン産生哺乳動物腺房細胞を、Exendin−4と接触させる工程を包含するプロセスによって作製される、インスリン産生細胞の集団を含む組成物であって、該Exendin−4が非インスリン産生細胞をインスリン産生細胞に分化させ得る、組成物。
- 前記非インスリン産生細胞がインビトロで前記増殖因子と接触される、請求項1に記載の組成物。
- 前記非インスリン産生細胞が人体を除くインビボで前記増殖因子と接触される、請求項1に記載の組成物。
- 前記非インスリン産生細胞が膵臓細胞を含む、請求項1に記載の組成物。
- 前記非インスリン産生細胞が膵臓腺房細胞を含む、請求項1に記載の組成物。
- 前記哺乳動物細胞がヒト細胞である、請求項1に記載の組成物。
- GLP−1レセプターを有する非インスリン産生哺乳動物腺房細胞をインスリン産生細胞に分化させる方法であって、該非インスリン産生哺乳動物腺房細胞を、Exendin−4と接触させる工程を包含し、該Exendin−4が、非インスリン産生細胞が人体でインビボで接触されることを除いて、非インスリン産生細胞をインスリン産生細胞に分化させ得るものである、方法。
- 前記非インスリン産生細胞が少なくとも24時間、前記増殖因子と接触される、請求項7に記載の方法。
- 前記非インスリン産生細胞がインビトロで前記増殖因子と接触される、請求項7に記載の方法。
- 糖尿病と診断された対象に増殖因子を投与してGLP−1レセプターを有する非インスリン産生哺乳動物腺房細胞と接触させることを包含する、糖尿病と診断された対象における糖尿病の治療のための医薬の製造におけるExendin−4の使用であって、該Exendin−4が、非インスリン産生細胞をインスリン産生細胞に分化させ得るものである、使用。
- GLP−1レセプターを有する哺乳動物膵臓アミラーゼ産生腺房細胞を、インスリンとアミラーゼとの両方を産生するように促進する方法であって、Exendin−4と該哺乳動物膵臓アミラーゼ産生腺房細胞を接触させる工程を包含し、該Exendin−4が、人体を除いて非インスリン産生細胞をインスリン産生細胞に分化させ得るものである、方法。
- I型糖尿病を有すると診断された被験体において糖尿病を処置するための医薬組成物であって、Exendin−4を包含し、該Exendin−4が、非インスリン産生細胞をインスリン産生細胞に分化させ得るものである、組成物。
- 前記Exendin−4の1日1回のボーラス投与に適する、請求項12に記載の組成物。
- 前記Exendin−4が、GLP−1レセプターを有する非インスリン産生細胞をインスリン産生細胞に分化させる、請求項12に記載の組成物。
- 前記非インスリン産生細胞が、前記増殖因子と少なくとも24時間接触される、請求項10記載の医薬品の製造における使用。
- 前記被検体が、I型糖尿病と診断される、請求項10〜12のいずれか1項記載の医薬品の製造における使用。
- 前記被検体が、II型糖尿病と診断される、請求項10〜12のいずれか1項記載の医薬品の製造における使用。
- 前記腺房細胞が、膵臓細胞である、請求項1〜6および12〜14のいずれか1項記載の組成物。
- 前記腺房細胞が、膵臓細胞である、請求項7〜9および11のいずれか1項記載の方法。
- 前記腺房細胞が、膵臓細胞である、請求項10および15〜17のいずれか1項記載の使用。
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JP2007114374A Expired - Fee Related JP4755133B2 (ja) | 1998-08-10 | 2007-04-24 | GLP−1またはExendin−4による、非インスリン産生細胞のインスリン産生細胞への分化、およびその使用 |
JP2009184807A Pending JP2009291206A (ja) | 1998-08-10 | 2009-08-07 | GLP−1またはExendin−4による、非インスリン産生細胞のインスリン産生細胞への分化、およびその使用 |
JP2011083828A Pending JP2011177181A (ja) | 1998-08-10 | 2011-04-05 | GLP−1またはExendin−4による、非インスリン産生細胞のインスリン産生細胞への分化、およびその使用 |
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JP2011083828A Pending JP2011177181A (ja) | 1998-08-10 | 2011-04-05 | GLP−1またはExendin−4による、非インスリン産生細胞のインスリン産生細胞への分化、およびその使用 |
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EP (2) | EP2028269B1 (ja) |
JP (4) | JP4624558B2 (ja) |
AT (1) | ATE445006T1 (ja) |
AU (1) | AU776514B2 (ja) |
CA (1) | CA2339326A1 (ja) |
DE (1) | DE69941510D1 (ja) |
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Families Citing this family (84)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7138486B2 (en) * | 1986-05-05 | 2006-11-21 | The General Hospital Corporation | Insulinotropic hormone derivatives and uses thereof |
US6703017B1 (en) | 1994-04-28 | 2004-03-09 | Ixion Biotechnology, Inc. | Reversal of insulin-dependent diabetes by islet-producing stem cells, islet progenitor cells and islet-like structures |
US6699973B1 (en) * | 1998-11-19 | 2004-03-02 | Elan Corporation, Plc | Antibodies to peptides that target GIT receptors and related methods |
US6242666B1 (en) * | 1998-12-16 | 2001-06-05 | The Scripps Research Institute | Animal model for identifying a common stem/progenitor to liver cells and pancreatic cells |
US6967019B2 (en) * | 1999-04-06 | 2005-11-22 | The Regents Of The University Of California | Production of pancreatic islet cells and delivery of insulin |
US6528486B1 (en) | 1999-07-12 | 2003-03-04 | Zealand Pharma A/S | Peptide agonists of GLP-1 activity |
US20030082155A1 (en) * | 1999-12-06 | 2003-05-01 | Habener Joel F. | Stem cells of the islets of langerhans and their use in treating diabetes mellitus |
US6448045B1 (en) | 2000-03-10 | 2002-09-10 | The Regents Of The University Of California | Inducing insulin gene expression in pancreas cells expressing recombinant PDX-1 |
EP1346722B1 (en) | 2000-12-01 | 2008-12-10 | Takeda Pharmaceutical Company Limited | Method for producing preparation containing bioactive substance |
DE60228972D1 (de) | 2001-07-31 | 2008-10-30 | Us Gov Health & Human Serv | Glp 1 exendin 4 peptidanaloga und deren verwendungen |
US6642003B2 (en) | 2001-08-02 | 2003-11-04 | Cedars-Sinai Medical Center | Human glucose-dependent insulin-secreting cell line |
US6911324B2 (en) | 2001-10-18 | 2005-06-28 | The Regents Of The University Of California | Induction of beta cell differentiation in human cells |
KR20050044393A (ko) * | 2001-11-09 | 2005-05-12 | 아르테셀 사이언스, 인크. | 지방 조직 유래된 스트로마 세포의 내분비 췌장 분화 및이의 용도 |
CA2471363C (en) | 2001-12-21 | 2014-02-11 | Human Genome Sciences, Inc. | Albumin fusion proteins |
US7635463B2 (en) | 2002-02-27 | 2009-12-22 | Pharmain Corporation | Compositions for delivery of therapeutics and other materials |
US20050260259A1 (en) * | 2004-04-23 | 2005-11-24 | Bolotin Elijah M | Compositions for treatment with glucagon-like peptide, and methods of making and using the same |
EP1478406B1 (en) * | 2002-02-27 | 2011-01-05 | PharmaIN Corporation | Compositions for delivery of therapeutics and other materials, and methods of making and using the same |
BR0311413A (pt) * | 2002-05-28 | 2005-03-22 | Becton Dickinson Co | Desenvolvimento e transdiferenciação de células acinares humanas |
WO2004050115A2 (en) * | 2002-12-03 | 2004-06-17 | Novo Nordisk A/S | Combination treatment using exendin-4 and thiazolidinediones |
EP1688148A1 (en) * | 2002-12-03 | 2006-08-09 | Novo Nordisk A/S | Combination treatment using exendin-4 and thiazolidinediones |
DE602004031927D1 (de) | 2003-02-04 | 2011-05-05 | Novo Nordisk As | Injektionsvorrichtung mit drehbarer dosiseinstellungsvorrichtung |
EP1636348B1 (en) * | 2003-06-20 | 2009-07-29 | Vrije Universiteit Brussel VUB | Method of generating islet beta-cells from exocrine pancreatic cells |
US9572840B2 (en) | 2003-06-27 | 2017-02-21 | DePuy Synthes Products, Inc. | Regeneration and repair of neural tissue using postpartum-derived cells |
PL1649013T3 (pl) | 2003-06-27 | 2016-07-29 | Depuy Synthes Products Inc | Regeneracja i naprawa chrząstki i kości z wykorzystaniem komórek poporodowych |
US9592258B2 (en) | 2003-06-27 | 2017-03-14 | DePuy Synthes Products, Inc. | Treatment of neurological injury by administration of human umbilical cord tissue-derived cells |
US8790637B2 (en) | 2003-06-27 | 2014-07-29 | DePuy Synthes Products, LLC | Repair and regeneration of ocular tissue using postpartum-derived cells |
CA2551324C (en) | 2004-01-06 | 2012-11-27 | Novo Nordisk A/S | Heteroaryl-ureas and their use as glucokinase activators |
DK2842576T3 (en) | 2004-01-21 | 2017-10-16 | Novo Nordisk Healthcare Ag | Transglutaminase-mediated peptide conjugation |
US20070231897A1 (en) * | 2004-06-03 | 2007-10-04 | Kyoto University | Induction of Insulin Secreting Cell |
KR101066882B1 (ko) | 2004-12-03 | 2011-09-26 | 트랜스테크 파르마, 인크. | 헤테로방향족 글루코키나제 활성화제 |
AU2006268589B2 (en) | 2005-07-14 | 2011-09-29 | Vtv Therapeutics Llc | Urea glucokinase activators |
NZ566799A (en) | 2005-09-14 | 2011-04-29 | Takeda Pharmaceutical | Dipeptidyl peptidase inhibitors for treating diabetes |
WO2007035629A2 (en) | 2005-09-16 | 2007-03-29 | Takeda Pharmaceutical Company Limited | Process for the preparation of pyrimidinedione derivatives |
CN101374946B (zh) | 2005-12-16 | 2017-07-18 | 伊西康公司 | 用于在组织相容性不匹配的移植中抑制有害的免疫反应的组合物和方法 |
KR101529318B1 (ko) | 2005-12-19 | 2015-06-16 | 파마인 코포레이션 | 치료제를 전달하기 위한 소수성 코어 담체 조성물, 이조성물의 제조 방법 및 그 조성물의 이용 방법 |
US9125906B2 (en) | 2005-12-28 | 2015-09-08 | DePuy Synthes Products, Inc. | Treatment of peripheral vascular disease using umbilical cord tissue-derived cells |
EP1996224B1 (en) | 2006-03-15 | 2012-11-07 | Novo Nordisk A/S | Mixtures of amylin and insulin |
US8324383B2 (en) | 2006-09-13 | 2012-12-04 | Takeda Pharmaceutical Company Limited | Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile |
TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
EP2099777B1 (en) | 2007-01-11 | 2015-08-12 | Novo Nordisk A/S | Urea glucokinase activators |
RU2413528C2 (ru) | 2007-01-18 | 2011-03-10 | Открытое Акционерное Общество "Валента Фармацевтика" | Лекарственный препарат для лечения сахарного диабета на основе экзенатида и даларгина, применение и способ лечения |
US8093236B2 (en) | 2007-03-13 | 2012-01-10 | Takeda Pharmaceuticals Company Limited | Weekly administration of dipeptidyl peptidase inhibitors |
CN101743252A (zh) | 2007-07-16 | 2010-06-16 | 诺沃-诺迪斯克有限公司 | 蛋白酶稳定化的、peg化的胰岛素类似物 |
US7960336B2 (en) | 2007-08-03 | 2011-06-14 | Pharmain Corporation | Composition for long-acting peptide analogs |
US8563527B2 (en) * | 2007-08-20 | 2013-10-22 | Pharmain Corporation | Oligonucleotide core carrier compositions for delivery of nucleic acid-containing therapeutic agents, methods of making and using the same |
US20090176892A1 (en) * | 2008-01-09 | 2009-07-09 | Pharmain Corporation | Soluble Hydrophobic Core Carrier Compositions for Delivery of Therapeutic Agents, Methods of Making and Using the Same |
US20110046071A1 (en) * | 2008-03-05 | 2011-02-24 | Tel Hashomer Medical Research Infrastructure And Services Ltd. | GLP-1 Receptor Agonists And Related Active Pharmaceutical Ingredients For Treatment Of Cancer |
DK2910570T3 (en) | 2008-03-18 | 2017-01-30 | Novo Nordisk As | Protease-stabilized acylated insulin analogues. |
CN105727261A (zh) | 2008-06-27 | 2016-07-06 | 杜克大学 | 包含弹性蛋白样肽的治疗剂 |
US10179900B2 (en) | 2008-12-19 | 2019-01-15 | DePuy Synthes Products, Inc. | Conditioned media and methods of making a conditioned media |
ES2665883T3 (es) | 2008-12-19 | 2018-04-30 | DePuy Synthes Products, Inc. | Tratamiento de enfermedades y trastornos pulmonares y pulmonares |
EP2411504B1 (en) | 2009-03-26 | 2017-05-10 | DePuy Synthes Products, Inc. | Human umbilical cord tissue cells as therapy for alzheimer's disease |
CN101991580B (zh) * | 2009-08-28 | 2013-03-20 | 杏辉天力(杭州)药业有限公司 | 以羊毛甾烷及茯苓萃取物治疗糖尿病的用途 |
US9445992B2 (en) | 2009-11-25 | 2016-09-20 | Arisgen Sa | Mucosal delivery compositions comprising a peptide complexed with a crown compound and/or a counter ion |
EA023925B1 (ru) | 2010-04-27 | 2016-07-29 | Зилэнд Фарма А/С | Пептидные конъюгаты агонистов рецептора glp-1 и их применение |
DK2569430T3 (en) | 2010-05-12 | 2019-02-04 | Univ Columbia | PROCEDURES FOR MANUFACTURING ENTEROENDOCRIN CELLS WHICH MANUFACTURE AND SECRET INSULIN |
JP6359972B2 (ja) | 2011-11-03 | 2018-07-18 | ジーランド ファーマ アクティーゼルスカブ | Glp−1受容体アゴニストペプチドガストリンコンジュゲート |
AU2012358810B2 (en) | 2011-12-23 | 2018-03-15 | DePuy Synthes Products, Inc. | Detection of human umbilical cord tissue-derived cells |
BR112015001451B1 (pt) | 2012-07-23 | 2022-03-29 | Zealand Pharma A/S | Composto, construção de ácido nucleico, vetor de expressão, célula hospedeira, composição farmacêutica, utilização de um composto ou de seu sal ou solvato farmaceuticamente aceitável |
TWI608013B (zh) | 2012-09-17 | 2017-12-11 | 西蘭製藥公司 | 升糖素類似物 |
UA116217C2 (uk) | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
ES2653765T3 (es) | 2012-12-21 | 2018-02-08 | Sanofi | Agonistas duales de GLP1/GIP o trigonales de GLP1/GIP/glucagón |
US9988429B2 (en) | 2013-10-17 | 2018-06-05 | Zealand Pharma A/S | Glucagon analogues |
MY176022A (en) | 2013-10-17 | 2020-07-21 | Boehringer Ingelheim Int | Acylated glucagon analogues |
EP3065767B1 (en) | 2013-11-06 | 2020-12-30 | Zealand Pharma A/S | Gip-glp-1 dual agonist compounds and methods |
AU2014345570B2 (en) | 2013-11-06 | 2019-01-24 | Zealand Pharma A/S | Glucagon-GLP-1-GIP triple agonist compounds |
WO2015086728A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/gip receptor agonists |
EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
TW201609799A (zh) | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | 雙重glp-1/gip受體促效劑 |
WO2015086730A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Non-acylated exendin-4 peptide analogues |
TW201625668A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 作為胜肽性雙重glp-1/昇糖素受體激動劑之艾塞那肽-4衍生物 |
TW201625670A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自exendin-4之雙重glp-1/升糖素受體促效劑 |
TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑 |
ES2854353T3 (es) * | 2014-04-22 | 2021-09-21 | Txp Pharma Gmbh | Análogos péptidicos con sonda(s) aminoacídicas ramificadas |
US9932381B2 (en) | 2014-06-18 | 2018-04-03 | Sanofi | Exendin-4 derivatives as selective glucagon receptor agonists |
EP3160503B1 (en) | 2014-06-26 | 2021-02-17 | The Trustees of Columbia University in the City of New York | Inhibition of serotonin expression in gut enteroendocrine cells results in conversion to insulin-positive cells |
RU2573933C1 (ru) | 2014-08-21 | 2016-01-27 | Дафот Энтерпрайсис Лимитед | Пептид для лечения сахарного диабета 2-го типа и его осложнений |
EP3212218B1 (en) | 2014-10-29 | 2021-06-30 | Zealand Pharma A/S | Gip agonist compounds and methods |
CA2980978A1 (en) | 2015-04-16 | 2016-10-20 | Zealand Pharma A/S | Acylated glucagon analogue |
AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
TW201706291A (zh) | 2015-07-10 | 2017-02-16 | 賽諾菲公司 | 作為選擇性肽雙重glp-1/升糖素受體促效劑之新毒蜥外泌肽(exendin-4)衍生物 |
DK3551651T3 (da) | 2016-12-09 | 2024-05-13 | Zealand Pharma As | Acylerede glp-1/glp-2-dobbeltagonister |
CN109679964A (zh) * | 2019-01-12 | 2019-04-26 | 青岛华义宏博生物科技有限公司 | 一种表达人胰岛素基因的重组乳酸乳球菌 |
US20220315632A1 (en) | 2019-03-15 | 2022-10-06 | Diet4Life Aps | Combination of dietary peptides |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5614492A (en) | 1986-05-05 | 1997-03-25 | The General Hospital Corporation | Insulinotropic hormone GLP-1 (7-36) and uses thereof |
US5545618A (en) | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
WO1993022427A1 (en) * | 1992-04-24 | 1993-11-11 | Somatix Therapy Corporation | Method of culturing viable cells and method of regulating the level of a compound in a body fluid |
CZ315594A3 (en) | 1992-06-15 | 1995-07-12 | Pfizer | Peptide of glucagon type, insulinotropic derivatives, process of their preparation, pharmaceutical composition containing such compounds and use |
NZ250844A (en) | 1993-04-07 | 1996-03-26 | Pfizer | Treatment of non-insulin dependant diabetes with peptides; composition |
US5424286A (en) * | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
CA2137206A1 (en) | 1993-12-09 | 1995-06-10 | John A. Galloway | Glucagon-like insulinotropic peptides, compositions and methods |
GB9409496D0 (en) * | 1994-05-12 | 1994-06-29 | London Health Ass | Method for improving glycaemic control in diabetes |
ATE417622T1 (de) * | 1996-08-08 | 2009-01-15 | Amylin Pharmaceuticals Inc | Regulation gastrointestinaler beweglichkeit |
WO1999043705A1 (en) * | 1998-02-27 | 1999-09-02 | Novo Nordisk A/S | N-terminally truncated glp-1 derivatives |
DE69911975T2 (de) | 1998-07-31 | 2004-09-09 | Novo Nordisk A/S | In-vitro stimulation von beta zellen vermehrung |
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ATE445006T1 (de) | 2009-10-15 |
EP1105460B1 (en) | 2009-10-07 |
JP2002522068A (ja) | 2002-07-23 |
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WO2000009666A2 (en) | 2000-02-24 |
JP2009291206A (ja) | 2009-12-17 |
DE69941510D1 (de) | 2009-11-19 |
JP4624558B2 (ja) | 2011-02-02 |
US7056734B1 (en) | 2006-06-06 |
EP2028269B1 (en) | 2015-10-21 |
ES2335066T3 (es) | 2010-03-18 |
JP2007209348A (ja) | 2007-08-23 |
ES2553108T3 (es) | 2015-12-04 |
JP2011177181A (ja) | 2011-09-15 |
US20070041951A1 (en) | 2007-02-22 |
WO2000009666A3 (en) | 2000-11-23 |
WO2000009666A9 (en) | 2000-07-13 |
AU5552499A (en) | 2000-03-06 |
DK1105460T3 (da) | 2010-02-08 |
EP1105460A2 (en) | 2001-06-13 |
AU776514B2 (en) | 2004-09-09 |
CA2339326A1 (en) | 2000-02-24 |
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