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US 2010/0075894 A1Published application
Reducing er stress in the treatment of obesity and diabetes
AssigneeHarvard University
InventorsGökhan S. Hotamisligil, Umut Özcan
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AssigneeHarvard University
InventorsGökhan S. Hotamisligil, Umut Özcan
Estimating the term…
Endoplasmic reticulum stress has been found to be associated with obesity. Therefore, agents that reduce or prevent ER stress may be used to treat diseases associated with obesity including peripheral insulin resistance, hypergylcemia, and type 2 diabetes. Two compounds which have been shown to reduce ER stress and to reduce blood glucose levels include 4-phenyl butyric acid (PBA), tauroursodeoxycholic acid (TUDCA), and trimethylamine N-oxide (TMAO). Other compounds useful in reducing ER stress are chemical chaperones such as trimethylamine N-oxide and glycerol. The present invention provides methods of treating a subject suffering from obesity, hyperglycemia, type 2 diabetes, or insulin resistance using ER stress reducers such as PBA, TUDCA, and TMAO. Methods of screening for ER stress reducers by identifying agents that reduce levels of ER stress markers in ER stressed cells are also provided. These agents may find use in methods and pharmaceutical compositions for treating obesity-associated diseases.
A method of treating or preventing a condition selected from the group consisting of obesity, insulin resistance, hyperglycemia, and type 2 diabetes, the method comprising:
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A method of treating or preventing obesity, the method comprising administering to a human an agent known to reduce ER stress.
A method of:
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A method of screening for agents to:
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A method of screening for agents that prevent ER stress, the method comprising steps of:
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A pharmaceutical composition comprising (1) an agent known to reduce ER stress, and (2) an agent selected from the group consisting of anti-diabetic agents, anti-obesity agents, antidyslipidemia agents, anti-atherosclerosis agents, and anti-hypertensive agents.
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A method of reducing ER stress or treating or preventing a disease associated with ER stress, the method comprising steps of:
A method of diagnosing insulin resistance, hyperglycemia, or type 2 diabetes, the method comprising:
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A method of modulating PERK, IRE-1a. JNK, IRS-1, IRS-2, Akt, or insulin receptor activity comprising:
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A method of increasing insulin action or insulin receptor signaling, the method comprising:
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A method of modulating insulin receptor signaling comprising:
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Dependencies are inferred from the claim text.