Metabolic Disease Treatments
The invention relates to the use of compounds to treat a number of conditions, such as a pre-diabetes condition, type 1 diabetes, type 2 diabetes, hyperglycemia, insulin resistance and glucose intolerance. Compounds that can be used in one or more of the treatment methods include 3β,7β,16α,17β-tetrahydroxyandrost-5-ene, 3α,7β,16α,17β-tetrahydroxyandrost-5-ene, 3β,7β,16α,17β-tetrahydroxyandrost-5-ene, 3β,16α,17β-trihydroxyandrost-5-ene-7-one, 3β,7β,17β-trihydroxy-17α-ethynylandrost-5-ene, 3β,17β-dihydroxy-17α-ethynylandrost-5-ene-7-one and 3β,7α,17β-trihydroxy-17α-ethynylandrost-5-ene.
1 . A method to treat hyperglycemia in a mammal having hyperglycemia comprising administering to the mammal an effective amount of a compound having the structure
wherein
R 1 is —OH, —SH, an ester, an ether or a thioether;
R 2 is —OH, ═O, an ester or an ether;
R 3 is —H, —OH, a halogen or an ester;
R 4 in the β-configuration is —OH or an ester;
R 4 in the α-configuration is —C≡C—(CH 2 ) n H, —C═CH—(CH 2 ) n H, —C≡C—(CH 2 ) n OH or —C═CH—(CH 2 ) n OH where n is 0, 1, 2, 3 or 4 when R 3 is —H or a halogen, or R 4 in the α-configuration is —H, —C≡C—(CH 2 ) n H, —C═CH—(CH 2 ) n H, —C≡C—(CH 2 ) n OH or —C═CH—(CH 2 ) n OH when R 3 is —OH or an ester;
R 5 is C 1-4 optionally substituted alkyl;
R 5 is —H or C 1-4 optionally substituted alkyl;
R 3 is —CHOH— or —CH(hydroxy ester)-; and
R 10 is —H or —F.
2 . The method of claim 1 wherein the compound has the structure
wherein R 4 in the α-configuration is —C≡CH or —C≡C—CH 3 .
3 . The method of claim 2 wherein the compound has the structure
wherein R 4 in the α-configuration is —C≡CH.
4 . The method of claim 3 wherein the mammal is a human.
5 . The method of claim 3 wherein the mammal has type 2 diabetes or has hyperglycemia associated with a trauma, optionally a hemorrhage or reperfusion injury, a cardiac surgery, a thermal burn or a chemical burn.
6 . The method of claim 1 wherein the compound has the structure
7 . The method of claim 6 wherein the compound has the structure
8 . The method of claim 7 wherein the mammal is a human.
9 . The method of claim 1 wherein the compound has the structure
10 . The method of claim 9 wherein the mammal has type 2 diabetes or has hyperglycemia associated with a trauma, optionally a hemorrhage or reperfusion injury, a cardiac surgery, a thermal burn or a chemical burn.
11 . The method of claim 10 wherein R 4 in the α-configuration is —H or —CCH.
12 . The method of claim 10 wherein R 4 in the β-configuration is —OH.