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First, lets look at the mechanism of glucose transport (thanks to wikipedia):
Insulin is the hormone which helps regulate glucose levels in the body. When blood glucose is high, insulin is released from the Islets of Langerhans. Insulin, among other things, will then facilitate the uptake of glucose into cells via increased expression and translocation of glucose transporter GLUT-4. Under conditions of exercise, however, blood sugar levels are not necessarily high, and insulin is not necessarily activated, yet muscles are still able to bring in glucose. AMPK seems to be responsible in part for this exercise-induced glucose uptake. Goodyear observed that with exercise, the concentration of GLUT-4 was increased in the plasma membrane, but decreased in the microsomal membranes, suggesting that exercise facilitates the translocation of vesicular GLUT-4 to the plasma membrane. While acute exercise increases GLUT-4 translocation, endurance training will increase the total amount of GLUT-4 protein available. It has been shown that both electrical contraction and AICAR treatment increase AMPK activation, glucose uptake, and GLUT-4 translocation in perfused rat hindlimb muscle, linking exercise-induced glucose uptake to AMPK. Chronic AICAR injections, simulating some of the effects of endurance training, also increase the total amount of GLUT-4 protein in the muscle cell.
Two proteins are essential for the regulation of GLUT-4 expression at a transcriptional level – myocyte enhancer factor 2 (MEF2) and GLUT-4 enhancer factor (GEF). Mutations in the DNA binding regions for either of these proteins results in ablation of transgene GLUT-4 expression. These results prompted a study in 2005 which showed that AMPK directly phosphorylates GEF, but it doesn’t seem to directly activate MEF2. AICAR treatment has been shown, however, to increase transport of both proteins into the nucleus, as well as increase the binding of both to the GLUT-4 promoter region.
There is another protein involved in carbohydrate metabolism that is worthy of mention along with GLUT-4. The enzyme hexokinase phosphorylates a six-carbon sugar, most notably glucose, which is the first step in glycolysis. When glucose is transported into the cell it is phosphorylated by hexokinase. This phosphorylation keeps glucose from leaving the cell, and by changing the structure of glucose through phosphorylation, it decreases the concentration of glucose molecules, allowing a gradient for more glucose to be transported into the cell. Hexokinase II transcription is increased in both red and white skeletal muscle upon treatment with AICAR. With chronic injections of AICAR, total protein content of hexokinase II increases in rat skeletal muscle.
And now cloning the expensive cardio in a pill, or rather cardio in a vial AICAR on the cheap:
We want:
1. AMP-K activation
2. Increase in GLUT-4 expression
3. Increase in Hexokinase II transcription
Metformin
Nr.1 check
Nr.2 check
Nr.3 check
It does all three, long available online, proven, oral and cheap. Why not more users?
Telmisartan
Nr.1. check
Nr.2. check ( **broken link removed** , Li L. Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator-Activated Receptor-? Activation. Diabetes : (2012) | Pubget )
Nr.3. Couldn't find the info
And a big PLUS: it is also a partial PPARδ activator, so it is like taking AICAR and GW501516 together (provided Nr.3 is true for Telmisartan too). Available online, cheap, proven. Again why aren't there more users?
OTC:
Policosanol
Nr.1 can be done with taking 20mg of Policosanol in the evening. OTC and cheap. Couldn't ask for more.
Nr.2 however is an issue as I have found no study that would show Policosanol increases GLUT-4 expression or at least MEF2 (as GEF is taken care of by AMPK directly). Should anyone be able to find any info on this, please feel free to share.
Nr.3 is the same no study in connection with Policosanol.
So if we want to make sure we get effect Nr.2 and Nr.3 we have to take supps for those too:
Nr.2: ALA, EGCG (both proven)
Nr.3: Bitter Melon Extract (never heard of it, feel free to add or comment)
Insulin is the hormone which helps regulate glucose levels in the body. When blood glucose is high, insulin is released from the Islets of Langerhans. Insulin, among other things, will then facilitate the uptake of glucose into cells via increased expression and translocation of glucose transporter GLUT-4. Under conditions of exercise, however, blood sugar levels are not necessarily high, and insulin is not necessarily activated, yet muscles are still able to bring in glucose. AMPK seems to be responsible in part for this exercise-induced glucose uptake. Goodyear observed that with exercise, the concentration of GLUT-4 was increased in the plasma membrane, but decreased in the microsomal membranes, suggesting that exercise facilitates the translocation of vesicular GLUT-4 to the plasma membrane. While acute exercise increases GLUT-4 translocation, endurance training will increase the total amount of GLUT-4 protein available. It has been shown that both electrical contraction and AICAR treatment increase AMPK activation, glucose uptake, and GLUT-4 translocation in perfused rat hindlimb muscle, linking exercise-induced glucose uptake to AMPK. Chronic AICAR injections, simulating some of the effects of endurance training, also increase the total amount of GLUT-4 protein in the muscle cell.
Two proteins are essential for the regulation of GLUT-4 expression at a transcriptional level – myocyte enhancer factor 2 (MEF2) and GLUT-4 enhancer factor (GEF). Mutations in the DNA binding regions for either of these proteins results in ablation of transgene GLUT-4 expression. These results prompted a study in 2005 which showed that AMPK directly phosphorylates GEF, but it doesn’t seem to directly activate MEF2. AICAR treatment has been shown, however, to increase transport of both proteins into the nucleus, as well as increase the binding of both to the GLUT-4 promoter region.
There is another protein involved in carbohydrate metabolism that is worthy of mention along with GLUT-4. The enzyme hexokinase phosphorylates a six-carbon sugar, most notably glucose, which is the first step in glycolysis. When glucose is transported into the cell it is phosphorylated by hexokinase. This phosphorylation keeps glucose from leaving the cell, and by changing the structure of glucose through phosphorylation, it decreases the concentration of glucose molecules, allowing a gradient for more glucose to be transported into the cell. Hexokinase II transcription is increased in both red and white skeletal muscle upon treatment with AICAR. With chronic injections of AICAR, total protein content of hexokinase II increases in rat skeletal muscle.
And now cloning the expensive cardio in a pill, or rather cardio in a vial AICAR on the cheap:
We want:
1. AMP-K activation
2. Increase in GLUT-4 expression
3. Increase in Hexokinase II transcription
Metformin
Nr.1 check
Nr.2 check
Nr.3 check
It does all three, long available online, proven, oral and cheap. Why not more users?
Telmisartan
Nr.1. check
Nr.2. check ( **broken link removed** , Li L. Telmisartan Improves Insulin Resistance of Skeletal Muscle Through Peroxisome Proliferator-Activated Receptor-? Activation. Diabetes : (2012) | Pubget )
Nr.3. Couldn't find the info
And a big PLUS: it is also a partial PPARδ activator, so it is like taking AICAR and GW501516 together (provided Nr.3 is true for Telmisartan too). Available online, cheap, proven. Again why aren't there more users?
OTC:
Policosanol
Nr.1 can be done with taking 20mg of Policosanol in the evening. OTC and cheap. Couldn't ask for more.
Nr.2 however is an issue as I have found no study that would show Policosanol increases GLUT-4 expression or at least MEF2 (as GEF is taken care of by AMPK directly). Should anyone be able to find any info on this, please feel free to share.
Nr.3 is the same no study in connection with Policosanol.
So if we want to make sure we get effect Nr.2 and Nr.3 we have to take supps for those too:
Nr.2: ALA, EGCG (both proven)
Nr.3: Bitter Melon Extract (never heard of it, feel free to add or comment)
