Compositions and methods for treating endocrine diseases and disorders
Disclosed herein are compounds and ligands, and compositions formed therewith, that modulate insulin secretion and suppress appetite by activating ectopic olfactory receptors. Also disclosed herein are methods for using the compositions to treat endocrine diseases, such as type-2 diabetes, and disorders, such as abnormal insulin secretion.
1. A composition for treating an endocrine disease of a patient, comprising:
a GLP-1/GIP secretion composition comprising (i) a delivery medium, (ii) at least a first receptor activating compound and (iii) at least a second receptor activating compound,
said first receptor activating compound adapted to bind to and activate at least one first receptor selected from the group comprising olfactory receptor family 51 subfamily E member 1 (OR51E1), olfactory receptor family 1 subfamily A member 1 (OR1A1), olfactory receptor family 2 subfamily C member 1 (OR2C1) and olfactory receptor family 10 subfamily J member 5 (OR10J5),
said second receptor activating compound adapted to bind to and activate at least one second receptor selected from the group comprising free fatty acid receptor 1 (FFAR1), free fatty acid receptor 4 (FFAR4), olfactory receptor family 2, subfamily W, member 1 (OR2W1), olfactory receptor family 2, subfamily B, member 11 (OR2B11), olfactory receptor family 2 subfamily J member 3 (OR2J3) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1),
said GLP-1/GIP secretion composition adapted to induce glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) secretion, and, thereby, increased insulin secretion in vivo, when said GLP-1/GIP secretion composition is delivered to said patient.
2. The composition of claim 1 , wherein said first receptor activating compound comprises 3-methylpentanoic acid.
3. The composition of claim 2 , wherein said 3-methylpentanoic acid comprises a first EC 50 value in said GLP-1/GIP secretion composition in the range of from about 5.0 μM to about 50.0 μM.
4. The composition of claim 1 , wherein said first receptor activating compound comprises eugenol.
5. The composition of claim 4 , wherein said eugenol comprises a second EC 50 value in said GLP-1/GIP secretion composition in the range of from about 0.5 μM to about 300.0 μM.
6. The composition of claim 1 , wherein said second receptor activating compound comprises a compound selected from the group consisting of a medium-chain free fatty acid, a long-chain free fatty acid and an omega-3 polyunsaturated fatty acid.
7. The composition of claim 6 , wherein said medium-chain free fatty acid comprises lauric acid.
8. The composition of claim 7 , wherein said lauric acid comprises a third EC 50 value in said GLP-1/GIP secretion composition in the range of from about 0.05 μM to about 0.5 μM.
9. The composition of claim 6 , wherein said long-chain free fatty acid comprises stearic acid.
10. The composition of claim 9 , wherein said stearic acid comprises a fourth EC 50 value in said GLP-1/GIP secretion composition in the range of from about 0.05 μM to about 0.5 μM.
11. The composition of claim 6 , wherein said omega-3 polyunsaturated fatty acid comprises alpha-linoleic acid.
12. The composition of claim 11 , wherein said alpha-linoleic acid comprises a fifth EC 50 value in said GLP-1/GIP secretion composition in the range of from about 0.01 μM to about 0.3 μM.
13. The composition of claim 6 , wherein said omega-3 polyunsaturated fatty acid comprises docosahexaenoic acid.
14. The composition of claim 13 , wherein said docosahexaenoic acid comprises a sixth EC 50 value in said GLP-1/GIP secretion composition in the range of from about 0.05 μM to about 0.4 μM.
15. The composition of claim 6 , wherein said omega-3 polyunsaturated fatty acid comprises eicosatetraenoic acid.
16. The composition of claim 15 , wherein said eicosatetraenoic acid comprises a seventh EC 50 value in said GLP-1/GIP secretion composition in the range of from about 0.01 μM to about 0.4 μM.
17. The composition of claim 1 , wherein said GLP-1/GIP secretion composition induces at least 50% activation of at least one of said OR51E1, said FFAR1 and said FFAR4 in vivo when said GLP-1/GIP secretion composition is said delivered to said patient.
18. The composition of claim 1 , wherein said delivery medium comprises glycerin-based water.
19. The composition of claim 1 , wherein said delivery medium comprises ingestible matter.
20. The composition of claim 19 , wherein said ingestible matter is selected from the group consisting of an item of food and a beverage.