G PROTEIN-COUPLED PURINERGIC RECEPTOR Gpr17 MEDIATES OREXIGENIC EFFECTS OF FOXO1 IN AGRP NEURONS
AssigneeThe Trustees of Columbia University in the City of New York
InventorsDomenico Accili, Hongxia Ren
Life of this patent
Estimating the term…
Abstract
G protein-coupled receptor (GPCR) Gpr17 expressed in hypothalamic Agouti-related peptide-expressing (AgRP) neurons increases appetite and glucose tolerance and insulin sensitivity. By contrast, increasing Gpr17 reduced glucose tolerance and increased appetite. Gpr17-agonists had no effect on FoxO1-deficient mice, indicating, together with other data, that Gpr17 is a Fox-O1 target. Certain embodiments are directed to methods for reducing appetite, increasing glucose tolerance and insulin sensitivity and treating diabetes by administering Gpr17 antagonists or inhibitory oligonucleotides. Appetite can be increased by administering Gpr17 agonists.
Claims25
A method, comprising
- a) identifying a subject in need of treatment for obesity,
- b) administering to the subject an agent that reduces Gpr17 expression or biological activity, in a therapeutically effective amount that reduces appetite thereby treating the obesity.
A method, comprising
- a) identifying a subject having impaired glucose tolerance or reduced insulin sensitivity,
- b) administering to the subject an agent that reduces Gpr17 expression or biological activity, in a therapeutically effective amount that increases glucose tolerance or insulin sensitivity, respectively, thereby treating the subject having impaired glucose tolerance or insulin sensitivity.
A method, comprising
- a) identifying a subject in need of treatment for an eating disorder associated with abnormal weight loss,
- b) administering to the subject a Gpr17 agonist in a therapeutically effective amount that increases the subject's appetite thereby treating the eating disorder.
A pharmaceutical formulation, comprising therapeutically effective amounts of a Gpr17 antagonist that binds to a purigenic receptor and an antagonist that binds to a cysteinyl-leukotriene (cysLT) receptor.
A pharmaceutical formulation, comprising therapeutically effective amounts of a Gpr17 agonist that binds to a purigenic receptor selected from the group comprising uracil nucleotides selected from the group consisting of UDP, UDP-glucose, and UDP-galactose and a Gpr17 agonist that binds to a cysteinyl-leukotriene (cysLT) receptor selected from the group consisting of LTC4, LTD4, and LTE4.
A method, comprising
- (a) providing a cell that overexpresses Gpr17,
- (b) determining a first level of pSTAT3 in the cell,
- (c) contacting the cell with a test compound under conditions and for a time sufficient to allow the test compound to interact with Gpr17,
- (d) determining a second level of pSTAT3 in the test cell at a predetermined time after contact with the test compound,
- (e) comparing the first and second levels of pSTAT3, and
- (f) if the second level is significantly higher compared to the first level, then identifying the test compound as a Gpr17 antagonist;
- and if the second level is significantly lower compared lower than the first level, then identifying the test compound as a Gpr17 agonist.
Dependencies are inferred from the claim text.