What Is AICAR Peptide?
AICAR or 5-Aminoimidazole-4-carboxamide ribonucleotide is a synthetic adenosine monophosphate analog. It works mainly by stimulating the AMP-dependent protein kinase (AMPK) activity. It is currently being used as a protective agent against ischemic damage in the cardiac myocytes in the event of cardiac injury.
The AMP-activated protein kinase is an enzyme and a protein that plays a regulatory role in several metabolic pathways. Its expression has been seen in several tissues, including the skeletal muscles, liver, and brain. In all these tissues, it has a net effect on lipogenesis. It inhibits cholesterol synthesis and ketogenesis. It modulates insulin secretion and skeletal muscle fatty acid oxidation with glucose uptake.
Several energy deficit states in the body can trigger the release of AMPK, like hypoxia or hypoglycemia. This process makes AICAR an important investigational peptide for its potential of being used as a treatment for diabetes. It has also been investigated for its role in reversing cardiac ischemic injury.
SYNONYMS: Z-nucleotide, 5-amino-4-imidazolecarboxamide ribotide, 5′-Phosphoribosyl-5-amino-4-imidazolecarboxamide
MOLECULAR WEIGHT: 338.213 g/mol
MOLECULAR FORMULA: C9H15N4O8P
Various studies have been conducted on the potential uses and benefits of AICAR. The following have been the most revolutionary:
Mitochondria are considered the powerhouse of the body. They serve as a platform for primary metabolic functions such as intracellular signaling and regulation of innate immunity. These processes are directly affected by mitochondrial senescence and ultimately alter cellular metabolism, inflammation, and even stem cell activity. These altogether reduce the pace of healing following an injury. That is how mitochondria are involved in age-related tissue and organ function decline. Any way of modulating mitochondrial activity can slow, cease or even reverse the process of aging.
A deficiency of NAD+ in the cell induces a pseudo-hypoxic state which interrupts signaling within the nucleus. Studies have provided evidence supporting the role of NAD+ supplementation in reversing at least some of the age-related decline in the function of mitochondria. The mechanism underlying this property involves the activation of the SIRT 1 function. A gene encodes an enzyme called Sirtuin-1 (NAD+ dependent Deacetylase Sirtuin-1). Sirtuin-1 regulates the mediators involved in metabolism, inflammation, the longevity of cells, and the processes linked to stress.
AICAR and The Heart
The incidence of cardiovascular disease in the modern world and the fatality associated are growing. This incidence makes it one of the most widely researched topics in the medical field. AICAR has been found to have a two-way protective role in protecting the heart from the ischemia associated with CVD.
Inflammation is a significant contributor to the disease pathology in atherosclerosis and other heart diseases. Research conducted on rabbits has proven that AICAR suppresses vascular smooth muscle proliferation. The control of vascular inflammation reduces the risk of short-term and long-term complications of stent placement. This process contributes to the overall health of the heart.
One of the immune responses that trigger a heart attack includes macrophage proliferation in response to high LDL (bad cholesterol) levels. AICAR plays a role in suppressing this immune response. Doing so mitigates the risk of precipitation of a heart attack.
If a heart attack does occur, AICAR plays a protective role, delaying the process of cell death by a process called preconditioning.
By this process, AICAR, in an ischemic heart, reduces the frequency and size of the infarct by up to 25%. It improves the overall blood flow to the heart.
AICAR and Insulin Resistance
Insulin resistance results from inflammation in the fatty tissues. This process results in raised blood glucose levels. The suppression of inflammation results in increased insulin sensitivity with improved glucose homeostasis. AICAR, via its anti-inflammatory role in different metabolic pathways, improves insulin sensitivity and lipid metabolism. In diabetic mice, AICAR administration showed reduced blood glucose levels without body weight changes.
AICAR mimics the effect that exercise has on glucose uptake by muscles. It upregulates the GLUT-4 receptors on muscles that are the prime transporters involved in glucose uptake.
AICAR and Cancer
AICAR, via its AMPK activation, plays a role in cancer cell metabolism. In research conducted on cell cultures and rats, prolonged AICAR administration slows down the metabolism of cancer cells and hence their proliferation. It also makes the cancerous cells more vulnerable to harsh environmental factors. This vulnerability makes AICAR suitable for cancer treatment adjunctive use with chemotherapeutic agents.
Thyroid cancer cell research has also shown that AICAR induces apoptosis in cancer cells by p21 induction and caspase 3 activations, causing inhibition of cancer cell proliferation.
AICAR and Fertility
For a very long time, a large amount of AICAR research has been directed toward its potential benefit in improving male fertility. Various studies on cats, dogs, and mice have shown that AMPK activation improves fertility. Since AICAR is an effective AMPK activator, its long-term administration leads to improved sperm motility. Since AICAR regulates the activity of all the active enzymes involved in sperm motility, its administration has a profound positive effect on fertilizing ability.
AICAR and its Anti-inflammatory Properties
AMPK activation has an overall anti-inflammatory effect at a cellular level. Inflammation forms a part of the pathogenesis of several diseases in the body. The same is valid for diabetes, making AICAR an effective anti-diabetic medication.
But its use as an anti-inflammatory in disease processes does not stop here. Animal research has shown its potential benefit in various inflammatory disorders like hepatitis, acute lung injury, asthma, colitis, and atherosclerosis.
To conclude, AICAR has significant cardioprotective properties. It improves metabolic health and complications associated with it. It finds use in cancer treatment and a variety of inflammatory conditions as well.