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WO1999044598A3 - Methods for inhibiting βcell apoptosis - Google Patents

Methods for inhibiting βcell apoptosis Download PDF

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Publication number
WO1999044598A3
WO1999044598A3 PCT/US1999/004730 US9904730W WO9944598A3 WO 1999044598 A3 WO1999044598 A3 WO 1999044598A3 US 9904730 W US9904730 W US 9904730W WO 9944598 A3 WO9944598 A3 WO 9944598A3
Authority
WO
WIPO (PCT)
Prior art keywords
methods
βcell
apoptosis
inhibiting
cell destruction
Prior art date
Application number
PCT/US1999/004730
Other languages
French (fr)
Other versions
WO1999044598A2 (en
Inventor
Roger H Unger
Michio Shimabukuro
Yan-Ting Zhou
Moshe Levi
Original Assignee
Univ Texas
Roger H Unger
Michio Shimabukuro
Zhou Yan Ting
Moshe Levi
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Texas, Roger H Unger, Michio Shimabukuro, Zhou Yan Ting, Moshe Levi filed Critical Univ Texas
Priority to AU28931/99A priority Critical patent/AU2893199A/en
Publication of WO1999044598A2 publication Critical patent/WO1999044598A2/en
Publication of WO1999044598A3 publication Critical patent/WO1999044598A3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention is directed to methods and compositions for preventing β-cell destruction and for ameliorating obesity related NIDDM. More particularly the present inventors have found that β-cell destruction occurs in obesity related NIDDM through the action of ceramides. The present invention suggests that ceramides mediate their cytotoxic influence through increased NO production. More particularly, the active agents for preventing β-cell destruction in obesity related NIDDM are troglitazone, leptin, triacsin and fumosinins, and no-production inhibitors, like aminoguanidines.
PCT/US1999/004730 1998-03-03 1999-03-03 Methods for inhibiting βcell apoptosis WO1999044598A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU28931/99A AU2893199A (en) 1998-03-03 1999-03-03 Fatty acid-induced beta-cell apoptosis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US7681898P 1998-03-03 1998-03-03
US60/076,818 1998-03-03

Publications (2)

Publication Number Publication Date
WO1999044598A2 WO1999044598A2 (en) 1999-09-10
WO1999044598A3 true WO1999044598A3 (en) 1999-11-04

Family

ID=22134367

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/004730 WO1999044598A2 (en) 1998-03-03 1999-03-03 Methods for inhibiting βcell apoptosis

Country Status (2)

Country Link
AU (1) AU2893199A (en)
WO (1) WO1999044598A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19921537A1 (en) * 1999-05-11 2000-11-23 Dieter Hoersch Treating carbohydrate metabolism disorders, especially diabetes, comprises activating insulin-secreting b-cells using glucagon-related peptide, glucose-dependent insulinotropic polypeptide, exendin-4 or related drugs

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997002004A2 (en) * 1995-06-30 1997-01-23 Eli Lilly And Company Methods for treating diabetes
WO1997010819A1 (en) * 1995-09-18 1997-03-27 Ligand Pharmaceuticals Incorporated Treating niddm with rxr agonists
WO1997023204A1 (en) * 1995-12-22 1997-07-03 Smithkline Beecham Plc Nitric oxide (no) synthase inhibitor to treat or prevent type ii diabetes
WO1998002159A1 (en) * 1996-07-12 1998-01-22 Smithkline Beecham Plc Novel treatment of leptine resistance
EP0849276A1 (en) * 1996-12-20 1998-06-24 Eli Lilly And Company Anti-obesity proteins

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997002004A2 (en) * 1995-06-30 1997-01-23 Eli Lilly And Company Methods for treating diabetes
WO1997010819A1 (en) * 1995-09-18 1997-03-27 Ligand Pharmaceuticals Incorporated Treating niddm with rxr agonists
WO1997023204A1 (en) * 1995-12-22 1997-07-03 Smithkline Beecham Plc Nitric oxide (no) synthase inhibitor to treat or prevent type ii diabetes
WO1998002159A1 (en) * 1996-07-12 1998-01-22 Smithkline Beecham Plc Novel treatment of leptine resistance
EP0849276A1 (en) * 1996-12-20 1998-06-24 Eli Lilly And Company Anti-obesity proteins

Non-Patent Citations (9)

* Cited by examiner, † Cited by third party
Title
FORMAN B M ET AL: "HYPOLIPIDEMIC DRUGS, POLYUNSATURATED FATTY ACIDS, AND EICOSANOIDS ARE LIGANDS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS ALPHA AND DELTA", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 94, no. 9, 29 April 1997 (1997-04-29), pages 4312 - 4317, XP000677599, ISSN: 0027-8424 *
MERRILL A.H. JR. ET AL: "Sphingolipids - The enigmatic lipid class: Biochemistry, physiology and pathophysiology.", TOXICOLOGY AND APPLIED PHARMACOLOGY, (1997) 142/1 (208-225)., XP002114145 *
MURPHY, JOHN E. ET AL: "Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin", PROC. NATL. ACAD. SCI. U. S. A. (1997), 94(25), 13921-13926, XP002114143 *
SHIMABUKURO M ET AL: "Fatty Acid-Induced Beta Cell Apoptosis: A Link Between Obesity and Diabetes", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 95, no. 95, March 1998 (1998-03-01), pages 2498 - 2502 2502, XP002099922, ISSN: 0027-8424 *
SHIMABUKURO, MICHIO ET AL: "Direct antidiabetic effect of leptin through triglyceride depletion of tissues", PROC. NATL. ACAD. SCI. U. S. A. (1997), 94(9), 4637-4641, XP002114142 *
SHIMABUKURO, MICHIO ET AL: "Leptin- or troglitazone-induced lipopenia protects islets from interleukin 1.beta. cytotoxicity", J. CLIN. INVEST. (1997), 100(7), 1750-1754, XP002114141 *
SHIMABUKURO, MICHIO ET AL: "Lipoapoptosis in beta-cells of obese prediabetic fa/fa rats. Role of serine palmitoyltransferase overexpression", J. BIOL. CHEM. (1998), 273(49), 32487-32490, XP002114147 *
SHIMABUKURO, MICHIO ET AL: "Role in nitric oxide in obesity -induced.beta. cell disease", J. CLIN. INVEST. (1997), 100(2), 290-295, XP002114144 *
UNGER R.H.: "How obesity causes diabetes in Zucker diabetic fatty rats.", TRENDS IN ENDOCRINOLOGY AND METABOLISM, (1997) 8/7 (276-282)., XP002114146 *

Also Published As

Publication number Publication date
WO1999044598A2 (en) 1999-09-10
AU2893199A (en) 1999-09-20

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WO1999044598A3 (en) Methods for inhibiting βcell apoptosis

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