Background
The development of new drugs for the treatment of diabetes mellitus (DM) is critically important. Insulin resistance (IR) is one of the main problems associated with type-2 DM (T2DM) seen in clinics. GW0742, a selective peroxisome proliferator-activated receptor (PPAR)-δ agonist, has been shown to ameliorate metabolic abnormalities including IR in skeletal muscle in mice fed high-fructose corn syrup. However, the influence of GW0742 on systemic insulin sensitivity has still not been elucidated. Therefore, it is important to investigate the effect of GW0742 on systemic IR in diabetic rats for the development of new drugs.
Biological Activity for GW 0742
GW 0742 is a potent and highly selective PPARδ agonist. EC50 values are 0.001, 1.1 and 2 μM for transactivation of human PPARδ, -α, and -γ receptors respectively. Neuroprotective in rat cerebellar granule neuronal cultures after brief (12-hour) exposure but exhibits inherent toxicity after prolonged (48-hour) incubation. Increases rate of fatty acid oxidation and protects against ischemia/reperfusion injury in neonatal and adult cardiomyocytes.
Description
GW0742 is a potent PPARβ and PPARδ agonist with IC50 of 1 nM for human PPARδ and EC50 of 1 nM, 1.1 μM and 2 μM for human PPARδ, PPARα and PPARγ, respectively. GW0742 (100 μM) activates human PPARα and mouse PPARβ in MCF-7 cells. GW0742 (100 μM) significantly reduces low KCl-induced apoptosis of cerebellar granule neurons. GW0742 shows no apparent intrinsic toxicity to cerebellar granule neuronal cells after 3-100 μM treatment for 24 hours, but induces an increase in cell death at 100 μM after 48 hours of treatment. Furthermore, GW0742 (100 μM) increases c-Jun expression in cerebellar granule neuron cultures observed at 6 hours. GW0742 (1 μM) induces PPARδ protein in neonatal rat cardiomyocytes. GW0742 also elevates long-chain acyl-CoA dehydrogenase (LCAD), very long-chain acyl-CoA dehydrogenase (VLCAD), acyl-CoA oxidase 1 (ACOX1), uncoupling protein 3 (UCP3), malondi Acyl-CoA decarboxylase (MCD) and pyruvate dehydrogenase kinase 4 (PDK4) in neonatal rat cardiomyocytes .
How Does GW0742 SARM Differ from Other SARMs?
As mentioned, GW0742 is not really a SARM. So, that's one way it differs right off the bat.
However, it differs in how it affects the body, as well.
GW0742 works similarly to SARMs in a couple of ways. First, it helps build lean muscle.
Second, it helps improve bone density. However, the real benefit of this drug is in how it affects fat in the body.
In that way, it works the same as any other PPAR on the market – it turns fat into a powerful source of energy for the body while dramatically increasing the oxidative capacity of muscle tissue.
What does that mean?
Simply put, it's well-suited for endurance athletes who need to keep their body fat low, but also need to ensure that their muscles are able to withstand extreme use.
Another way that GW0742 SARM differs from other drugs on the market is that it affects insulin sensitivity in the body.
It is currently being investigated as a potential treatment for Type 2 diabetes in at least one clinical trial involving laboratory rats.2
In comparison, conventional SARMs only build lean muscle mass, enhance strength, and improve bone density.
However, the problem here is one of evidence.
There have been no human trials of any kind with GW0742, which means there is no accurate evidence of its effectiveness.
How Does GW0742 SARM Work?
The operation of GW0742 SARM in the body is not clear due to a complete lack of human testing.
However, it is thought that it acts similarly to Cardarine, which has seen more extensive animal testing, but no human testing.
Both drugs are considered investigatory only and are not approved for use in humans.
If GW0742 SARM works similarly to Cardarine, it improves the gene expression that stimulates fat metabolism within the body.
This allows it to accelerate fat loss and means that your cutting efforts will yield much more significant results.
It can allow bodybuilders to achieve the ripped physique they want, with better vascularity and much more defined musculature.
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