AICAR is a 5-aminoimidazole 4-carboxamide ribonucleotide intermediate generation of the chemical inosine monophosphate. This may also be produced under the name ZMP. AICAR was designed to stimulate AMP-dependent protein kinase or AMPK activity which has been used in research, as a means of controlling ischemic injury in cardiac structures that could lead to a myocardial infarct, due to insufficient blood flow to the myocardium.
AICAR may also be produced under the name acadesine because it is of the adenosine chemical, which enters the cardiac cells as a means of inhibiting adenosine kinase and deaminase. This can be used by an animal’s body to enhance nucleotide resynthesis and increase adenosine generations throughout the adenosine monophosphate structures. However, these effects only appear if the proper conditions are present for myocardial ischemia in the animal.
Effects on Insulin Stimulated Glucose Uptake
Physical activity can increase insulin action within skeletal muscles and data, indicating that AICAR can trigger the mechanisms that are behind this effect at the molecular level.
AICAR can trigger AMPK, and a study worked to understand how this effects insulin stimulated glucose uptake, following long-term exercise. Chronic administration of AICAR was also investigated, following fiber specific changes of insulin signaling and GLUT-4 expression.
Rats were placed into sedentary, exercise groups worked on treadmills and groups exposed to AICAR. AMPK activity as well as glucose transport, GLUT-4 expression and insulin signaling were measured throughout the muscle tissue by fiber composition.
Groups exposed to AICAR and exercise saw a fiber specific glucose transport increase which was accompanied by higher GLUT-4 expression.
Insulin signaling was only improved after AICAR was administered; these improvements were not fiber specific. This implies that chronic administration of AICAR as well as a long term exercise program can improve insulin stimulated glucose transport in the skeletal muscles.
Apparent Enhancement of Liver and Muscle Insulin Action
Exercise is found to improve sensitivity to insulin. AMPK is vital to controlling the metabolism during exercise.
A study was performed to determine if AICAR could control insulin actions on rats with a high fat diet, compared to those who were given insulin administrations.
Glucose infusion rates for rats exposed to AICAR were shown to improve in white quadriceps, but not in red. AICAR also produced a reduced malonyl-CoA response in the muscles and liver.
Research has not yet determined how AICAR affects insulin, but follow up studies imply that some post AICAR administration effects on insulin are standard in normal rats. This is believed to be due to the pharmacological activation of the AMPK output in the rat’s body. This action may have potential in treating type 2 diabetes in animals with insulin resistance.
Inhibition of Lipolysis and Lipogenesis
Hormone sensitive lipase in vivo has been shown to phosphorylate on sites, known as the basal and regulatory sites.
The intracellular role of basal sites or the protein kinase that occurs here is still unknown.
AICAR has been shown to elevate AMPK in these cells, but the reaction is administration dependent.
Applying AICAR has inhibited lipogenesis in the ACC, which appears to be essential to the regulation of lipogenesis. AMPK also appears to play a steady role in antillipolyic regulating of HSL in rats.
Most AICAR research focuses on the potential for this chemical to improve protective preconditioning, prior to a myocardial infarction. This may delay the death of cells in this area, to encourage recovering and survival of the animal after this event takes place.
AICAR can also be applied during ischemia, if necessary. This is an anti-inflammatory response because it discourages production of the endothelial nitric oxide synthase. This preconditioning is mediated by AMPK and hemoxygenase dependent mechanisms.