Enolase 1 (Eno1) compositions and uses thereof
View Patent ↗The invention provides compositions comprising Eno1 for delivery to a muscle. Further, the invention provides a method for normalizing blood glucose in a subject with elevated blood glucose, comprising administering to the subject enolase 1 (Eno1), thereby normalizing blood glucose in the subject. The invention also provides methods of treating one or more conditions including impaired glucose tolerance, insulin resistance, pre-diabetes, and diabetes, especially type 2 diabetes in a subject, comprising administering to the subject enolase 1 (Eno1), thereby treating the condition in the subject. In certain methods of the invention, the Eno1 is delivered to muscle.
1. A method of decreasing blood glucose in a subject with elevated blood glucose, the method comprising administering to the subject a pharmaceutical composition comprising Enolase 1 (Eno1) or a fragment thereof, thereby decreasing blood glucose in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
2. A method of increasing glucose tolerance in a subject with decreased glucose tolerance, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby increasing glucose tolerance in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
3. A method of improving insulin response in a subject with decreased insulin sensitivity and/or insulin resistance, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby improving insulin response in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
4. A method of treating diabetes in a subject, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby treating diabetes in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
5. The method of claim 4 , wherein the diabetes is type 2 diabetes or type 1 diabetes.
6. The method of claim 4 , wherein the diabetes is pre-diabetes.
7. A method of decreasing an HbA1c level in a subject with an elevated HbA1c level, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby decreasing the HbA1c level in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
8. A method of improving blood glucose level control in a subject with abnormal blood glucose level control, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby improving blood glucose level control in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
9. The method of claim 1 , wherein glucose flux in a skeletal muscle cell of the subject is increased.
10. A method of increasing glucose flux in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising Eno1or a fragment thereof, thereby increasing glucose flux in the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
11. A method of increasing glycolytic activity or capacity in a skeletal muscle cell of a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby increasing glycolytic activity or capacity in a skeletal muscle cell of the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
12. A method of increasing mitochondrial free fatty acid oxidation in a skeletal muscle cell of a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising Eno1 or a fragment thereof, thereby increasing mitochondrial free fatty acid oxidation in a skeletal muscle cell of the subject, wherein the Eno1 or a fragment thereof has glycolytic activity and is present in a therapeutically effective amount.
13. The method of any one of claims 1 , 2 , 3 , 4 , 7 , 8 , 10 , 11 and 12 , wherein the Eno1 is administered parenterally.
14. The method of any one of claims 1 , 2 , 3 , 4 , 7 , 8 , 10 , 11 and 12 , wherein the Eno1 is administered orally.
15. The method of claim 13 , wherein the Eno1 is administered by a route selected from the group consisting of intramuscular, intravenous, and subcutaneous.
16. The method of any one of claims 1 , 2 , 3 , 4 , 7 , 8 , 10 , 11 and 12 , wherein the subject has any one or more of elevated blood glucose, decreased glucose tolerance, decreased insulin sensitivity and/or insulin resistance, diabetes, elevated HbA1c level, and abnormal blood glucose level control.
17. The method of claim 1 , further comprising selecting a subject having any one or more of elevated blood glucose, decreased glucose tolerance, decreased insulin sensitivity and/or insulin resistance, diabetes, elevated HbA1c level, and abnormal blood glucose level control.
18. The method of any one of claims 1 , 2 , 3 , 4 , 7 , 8 , 10 , 11 and 12 , wherein the subject is human.