AICAR or 5-aminoimidazole 4-carboxamide ribonucleotide is commonly produced under the name adenosine. This chemical will enter the cardiac cells, after it is administered in an animal’s body, as a means of inhibiting adenosine deaminase and adenosine kinase. This helps to enhance the rate that the nucleotide re-synthesis increases the adenosine generation from the adenosine monophosphate.
AICAR only elicits this reaction when it is present during myocardial ischemia conditions in animals, though this reaction can be both normal and induced for the sake of research purposes. When applied to cardiac myocytes, the AICAR peptide is phosphorylated to an AICA-ribiotide formula that will activate AMPK without the need to alter the nucleotide levels in the nearby tissue.
This allows AICAR to enter de novo synthesis pathways as a means of causing adenosine synthesis and inhibiting adenosine deaminase. This can cause an increase in the levels of adenosine and ATP.
Long Term Administration Prevents Diabetes
Implementing lifestyle changes, including exercise programs, is essential to preventing diabetes, as well as implementing AMPK, to benefit the effects of exercise on the lipid metabolism.
Effects of a long term exercise regimen as well as the application of AICAR treatments were created in order to activate AMPK activators. These results were viewed on Zucker male diabetic fatty rats.
Five week old rats with pre-diabetic conditions were given daily runs on a treadmill or AICAR throughout 8 weeks and these effects were compared to those that did not receive treatment.
The treated groups did not develop hyperglycemia symptoms during the period of intervention while insulin sensitivity throughout the body saw an increase in those that were exposed to AICAR.
In addition to these results the morphology of the pancreas was normal which indicates that AMPK activation could help to preserve this cell function.
Activating Glycogen Phosphorylase and Glycogenolysis
To determine the permeable molecular structure of AICAR and their metabolite activities on AMPK, the glycogen metabolism in the rat seleus muscle preparations were compared in vitro.
The base of this insulin stimulation was studied via the rates of the radiochemical lactate formation as well as the glycogen and net lactate release.
AICAR was shown to stimulate the net lactate release but not the other conditions. This alteration was only effective on the basal concentration of the insulin.
This increased rate of glycogenolysis may have caused the increased net lactate release because this causes the net lactate release as glycogen phophorylase. This activity is noticeably improved by the presence of AICAR.
Inhibiting Lipolysis and Lipogenesis
Hormone sensitive lipase has been shown to cause phosphorylated on two sites, known as the regulatory and basal sites.
The intracellular role of basal sites to identify protein kinase phosphorylating if the site has not been established.
Applying AICAR has been found to increase AMPK reactions but these effects are dependent on applications of the chemical. Preincubation of the adipocytes of AICAR cause a reduction in the response of the cells in the liplytic agenst of isoprenaline.
AICAR has also been found to distinctly inhibit the lipogenesis throughout the increased phosphorylation of the ACC or acetyl CoA carboxylase. This has led to the belief that while it is necessary to regulate lipogenesis, AMPK is essential to managing antilipolytic roles that will help to regulate HSL in rats.
AIRCAR preconditioning for tissues must be mediated using ATP sensitive potassium channel as well as hemeoxygenase dependent mechanisms. This will increase the AMPK dependent recruitment of the K channels to sarcolemma, causing the action potential duration to be shorter. This will decrease the calcium overload that the body is forced to manage to further decrease inflammation. This preconditioning has been shown to be effective for up to 2 hours in rabbits.