Compositions and methods for regulating pancreatic beta cell function using adipsin
AssigneeDana-Farber Cancer Institute, Inc.
InventorsBruce M. Spiegelman, James Lo
Life of this patent
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Abstract
The present invention provides compositions and methods for regulating pancreatic beta cell function through modulation of adipsin activity and/or expression. Also provided are methods for preventing, treating, diagnosing, and prognosing metabolic disorders, such as diabetes, in a subject through modulation or detection of adipsin activity and/or expression.
Claims28
1-27. (canceled)
A method of monitoring pancreatic beta cell dysfunction in a subject, the method comprising:
- a) determining the copy number, level of expression, or level of activity of adipsin in a first subject sample at a first point in time;
- b) repeating step a) during at least one subsequent point in time;
- and
- c) comparing the copy number, level of expression, or level of activity of said one or more biomarkers detected in steps a) and b);
- wherein a decreased copy number, a significantly decreased level of expression, or a significantly decreased level of activity of the one or more biomarkers in the first subject sample relative to at least one subsequent subject sample indicates pancreatic beta cell dysfunction optionally wherein
- i) the first subject sample is obtained from the subject prior to, concurrently with, or after administration of one or more treatments for a pancreatic beta cell disorder;
- and/or
- ii) between the first point in time and the subsequent point in time, the subject has undergone treatment, completed treatment, and/or is in remission for a pancreatic beta cell disorder.
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A method of prognosing pancreatic beta cell failure in a subject or diagnosing a subject afflicted with a pancreatic beta cell disorder, the method comprising:
- a) determining the copy number, level of expression, or level of activity of adipsin in a subject sample;
- b) determining the copy number, level of expression, or level of activity of adipsin in a control sample or a predetermined reference;
- and
- c) comparing the copy number, level of expression, or level of activity of adipsin in steps a) and b);
- wherein a decrease in the copy number, a significantly decreased level of expression, or a significantly decreased level of activity of adipsin in the subject sample relative to the copy number, level of expression, or level of activity of adipsin in the control sample or predetermined reference indicates a positive prognosis for pancreatic beta cell failure in the subject or indicates the subject is afflicted with a pancreatic beta cell disorder
(canceled)
A method of assessing the efficacy of an agent for treating a pancreatic beta cell disorder in a subject, comprising:
- a) determining in a first subject sample contacted with the agent or maintained in the presence of the agent the copy number, level of expression, or level of activity of adipsin;
- b) determining the copy number, level of expression, or level of activity of adipsin in at least one subsequent subject sample maintained in the absence of the test compound, or repeating step a) during at least one subsequent point in time after administration of adipsin;
- and
- c) comparing the copy number, level of expression, or level of activity of adipsin,
- wherein a decreased copy number, a significantly decreased level of expression, or a significantly decreased level of activity of adipsin in the first subject sample relative to at least one subsequent subject sample, indicates that the agent treats the pancreatic beta cell disorder in the subject, optionally wherein between the first point in time and the subsequent point in time, the subject has undergone treatment, completed treatment, and/or is in remission for the pancreatic beta cell disorder.
36-37. (canceled)
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49-50. (canceled)
Dependencies are inferred from the claim text.