Aicar Reduction of Metabolic Disturbances

AICAR refers to 5-Aminoimidazole 4-carboxamide ribonucleotide, which is an intermediate inosine monophosphate. This may also be referred to as ZMP which is an analog of AMP that can create AMP-dependent protein kinase activity in animal tissues. Clinically, AICAR is being investigated as a potential pharmaceutical tool for managing cardiac ischemic injury, though testing on humans is not yet recommended.

If cardiac ischemic injuries are not treated they may lead to a myocardial infarct. This condition is caused by insufficient oxygen and blood flow to the myocardium. AICAR was first developed in the 1980s as a means of preserving this blood flow, particularly in animals that were undergoing surgery in laboratory testing for other experiments.

This chemical has also been shown to increase metabolic activity when it is administered in clinical studies, which can alter the composition of muscle tissues.

Exercise has been found to improve insulin sensitivity and AMP activated protein kinase has an important role in effective muscle mechanisms during exercise.

In order to investigate the roles that this chemical has in on insulin actions, high fat fed rats were given subcutaneous injections of saline or AICAR.

This was used during a glucose infusion rate clamp method to enhance the HF-AIC when compared with the HF con rats.

Those that were insulin stimulated saw a glucose uptake that was improved but red quadriceps did not see improvement.

Single applications of AICAR effects on insulin action have yet to be determined. Follow up studies indicate that these effects also occur in normal rats.

Reduction of Metabolic Disturbances

Chemical activation of AMP activated protein kinase, using adenosine analogs AICAR, is known to augment insulin action as well as upregulate mitochondrial enzymes in the skeletal muscles.

Acute exposure to AICAR has been found to reduce fatty acidsynthesis and sterol in the hepatocytes incubated in vitro in rats. This is particular during euglycemic clamp conditions.

In order to investigate whether or not this chronic administration would be beneficial to those with insulin sensitivity and whether or not this would be capable of insulin resistance syndrome.

Results indicated that AICAR administration could increase maximum insulin stimulated glucose transport. This could increase the tolerance of a lipid profile while reducing systolic blood pressure in animals.

Studies were designed to determine how the metabolic and histological effects of administering AICAR for 14 days.

AICAR treatment can cause a significant decrease in the presence of IIB fibers as well as an increase in the percentage of IIX fibers found throughout extensor digitorum longus muscle.

AICAR applications do not appear to alter the capillary to fiver ratio with regular applications. These applications are found to increase glycolytic as well as oxidative enzyme activities but this did not have an impact on the increase of antioxidant enzyme activities.

AICAR treatments can increase uncoupling of proteins in the EDL as well as peroxisome proliferator activated receptor protein levels in EDL muscles. By contrast, myogenin levels have not been altered with applications of AICAR in animal test subjects. These results imply that the chronic activation of AMPK caused by the application of AICAR can alter the muscle histochemical as well as metabolic characteristsics.

AICAR has been shown to assist with arterial occlusion when it is applied via reperfusion before prolonged ischemia. This is known as preconditioning and in studies has been shown to be effective in protecting the tissues from long-term damage.

This can help to delay the death of cells so more of the tissue can be salvaged after the myocardium around reperfusion therapy. AICAR has been shown to be effective in triggering anti-inflammatory effects in the heard before the endothelial nitric oxid synthase.