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Secreted ap2 and methods of inhibiting same

a technology of ap2 and ap2 protein, which is applied in the field of secreted ap2, can solve the problems of increasing the risk of clotting, and achieve the effects of reducing the amount of ap2 protein, reducing the symptom of metabolic disease, and reducing glucose intoleran

Inactive Publication Date: 2012-05-31
PRESIDENT & FELLOWS OF HARVARD COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0003]The invention is based on the discovery that serum aP2 regulates systemic insulin sensitivity and glucose metabolism. Accordingly, a method of reducing a symptom of metabolic disease is carried out by administering to a subject a composition that binds to and blocks aP2 in the circulation (e.g., blood or serum aP2), by administering a composition that binds to and reduces the amount of aP2 protein in circulation, or by administering an inhibitor of aP2 secretion by a cell. For example, glucose intolerance is reduced following administration of such an inhibitor. Exemplary compositions include antibodies or antigen-specific fragments thereof, small molecules that bind to aP2, as well as compositions that inhibit secretion of aP2 by an adipocyte or macrophage.

Problems solved by technology

The main features of metabolic syndrome include insulin resistance, hypertension (high blood pressure), cholesterol abnormalities, and an increased risk for clotting.
Patients with this cluster of risk factors are most often overweight or obese.

Method used

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  • Secreted ap2 and methods of inhibiting same
  • Secreted ap2 and methods of inhibiting same
  • Secreted ap2 and methods of inhibiting same

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Embodiment Construction

[0061]aP2 is also known as Adipocyte Fatty Acid Binding Protein (AFABP), Fatty Acid Binding Protein-4 (FABP-4), and Adipocyte Lipid Binding Protein (ALBP). Prior to the invention, aP2 was considered a cytosolic protein. Secreted adipose lipid chaperon, aP2, has now been found to regulate liver glucose metabolism. aP2 was found to be an adipose-secreted protein in cells of mice and other mammals such as humans.

[0062]Serum aP2 regulates systemic glucose metabolism. A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of aP2 secretion by a cell or by administering an aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Compositions inhibit secretion of aP2 by an adipocyte or macrophage. Alternatively, exemplary compositions such as antibodies bind to circulating aP2, thereby reducing the level or activity of a...

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Abstract

A method of reducing a symptom of a clinical disorder characterized by aberrantly elevated circulating aP2 is carried out by administering to a subject an inhibitor of secreted aP2, secretion of aP2, or a serum aP2 blocking agent. For example, glucose intolerance is reduced following administration of such an inhibitor or agent. Exemplary compositions inhibit cellular secretion of aP2 or bind to circulating aP2, thereby reducing the level or activity of aP2 in blood or serum.

Description

STATEMENT OF GOVERNMENT INTERESTS[0001]This invention was made with government support under DK064360 and DK071507 awarded by the National Institutes of Health. The government has certain rights in the invention.BACKGROUND OF THE INVENTION[0002]Metabolic syndrome or metabolic disease is a term that defines a cluster of metabolic risk factors that come together in a single individual and lead to diabetes and cardiovascular disease. The main features of metabolic syndrome include insulin resistance, hypertension (high blood pressure), cholesterol abnormalities, and an increased risk for clotting. Insulin resistance refers to the diminished ability of cells to respond to the action of insulin in promoting the transport of the sugar glucose, from blood into muscles and other tissues. Patients with this cluster of risk factors are most often overweight or obese.SUMMARY OF THE INVENTION[0003]The invention is based on the discovery that serum aP2 regulates systemic insulin sensitivity and ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61P3/00A61P3/04A61P25/00A61P1/16A61P9/10A61P11/06A61P9/12G01N33/566A61P3/10
CPCA61K2039/505C07K16/18C07K2317/76C07K2317/34C07K14/47A61P1/16A61P11/00A61P11/06A61P11/16A61P25/00A61P25/28A61P3/00A61P3/04A61P31/18A61P3/06A61P3/08A61P43/00A61P5/00A61P7/00A61P9/00A61P9/10A61P9/12A61P3/10
Inventor HOTAMISLIGIL, GOKHAN S.CAO, HAIMING
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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