The AICAR nucleotide appears to comprise one ribose sugar, phosphate group, and adenine base. It is considered an essential nucleotide in cellular energy metabolism and may be a precursor to adenosine monophosphate (AMP). Studies suggest that AICAR may stimulate the metabolic enzyme AMP-activated protein kinase (AMPK).
Research suggests that AICAR may improve glucose tolerance, insulin sensitivity, and glucose absorption in skeletal muscle via activating AMPK. Animal studies have suggested that AICAR may enhance physical activity, and there is speculation that it may also have anti-inflammatory properties.
AICAR Peptide Research and Investigations
AICAR Peptide and Organs
Researchers speculate that AICAR may protect organs from damage caused by ischemia and reperfusion. Animal studies on myocardial ischemia-reperfusion damage have suggested that this nucleotide may decrease infarct size and enhance heart function. Key factors to reperfusion damage, including oxidative stress and inflammation, may be mitigated by AICAR’s potential to activate AMPK. [i]
Researchers hypothesize that after coronary artery bypass graft (CABG) surgery, many test subjects have problems that AICAR may mitigate. [ii] The studies conducted were placebo-controlled and double-blind. Myocardial infarction during surgery, cardiac mortality up to day 4 after surgery, and cardiac arrest, stroke, and death were all predicted to be reduced with AICAR. Further findings suggested that AICAR may decrease the need for ventricular-assistance devices in subjects with severe surgical heart failure.
AICAR’s protective properties may extend beyond the liver. The action of the AMPK activator AICAR on a rat model of ethanol-induced hepatic steatosis was studied. [iii] The research suggested continuous ethanol feeding led to a histologically and biochemically fatty liver, but AICAR appeared to mitigate this change. One study suggested that AICAR may inhibit triglyceride production by decreasing rats’ hepatic SREBP-1c and FAS expression.
AICAR Peptide and Insulin Sensitivity
Activating AMPK inside cells and causing them to pull in glucose has suggested promise in studies that AICAR may reduce blood sugar and enhance insulin sensitivity. One experiment with animals looked at whether or not AICAR may improve glucose transport in horse skeletal muscle. [iv] At first glance, AICAR seemed to lower blood glucose and raise insulin concentration without influencing lactate levels. The ratio of phosphorylated to total AMPK in skeletal muscle was also speculated to rise due to AICAR, as did the production of GLUT8 proteins.
A clinical experiment also investigated the potential for AICAR to increase glucose absorption in muscle. [v] A total of 29 male subjects were recruited in the research. The findings suggested that AICAR and physical activity may have increased AMPK activation and glucose absorption in skeletal muscle. The results suggested that glucose absorption in muscle may be improved by AICAR plus physical activity and that AICAR may improve whole-organism glucose disposal. The phosphorylation of extracellular signal-regulated kinase 1/2 was also hypothesized to be affected by AICAR.
Researchers speculated that AICAR might decrease plasma-free fatty acid content, hepatic glucose production, and blood glucose concentrations in an experiment including 10 male subjects with type 2 diabetes. Researchers suggested an increase in acetyl-CoA carboxylase phosphorylation in skeletal muscle but no increase in AMPK phosphorylation.
AICAR Peptide and Endurance
Studies suggest the activation of AMP-activated protein kinase, glycogen phosphorylase, fructose-1, and 6-bisphosphatase may have all been linked to AICAR. [vi] According to some research, these activations seem to increase oxidative metabolism and mitochondrial biogenesis. Muscle endurance may improve with increased mitochondrial number and function. One study suggested that AICAR may increase running endurance in inactive mice by 44% and activate metabolic genes. This study suggests peptides might target the AMPK-PPARdelta pathway [vii].
A similar finding was speculated in another animal study [viii]: “Mice given an agonist of the AMP-activated protein kinase showed an increase in endurance compared to exercise-trained controls.” Researchers also speculate that AICAR may improve muscle function and increase exercise tolerance in a mouse model of Duchene muscular dystrophy, likely through inducing autophagy. [ix] Scientists hypothesized that limb blood flow might have increased proportionally with AICA-riboside infused, although skeletal muscle glucose absorption did not seem to be affected. It was reported by the research team that nitric oxide appeared to mediate the improvement in blood flow as an inhibitor of endothelial NO synthase appeared to reduce the improvement. [x]
More investigation is required to explore its potential in scientific research, and these studies must continue. Only academic and scientific institutions are allowed to use AICAR peptides. If you are a licensed professional interested in buying peptides for your clinical studies, visit this website.
Please note that none of the items mentioned are approved for human or animal ingestion. Laboratory research compounds are only for in-vitro and in-lab use. Any kind of physical introduction is illegal. Only authorized professionals and working scientists may make purchases. The content of this article is intended only for educational purposes.
References:
[i] Cieslik, K. A., Taffet, G. E., Crawford, J. R., Trial, J., Mejia Osuna, P., & Entman, M. L. (2013). AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction. Journal of molecular and cellular cardiology, 63, 26–36. https://doi.org/10.1016/j.yjmcc.2013.07.005 [ii] Mangano D. T. (1997). Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. The Multicenter Study of Perioperative Ischemia (McSPI) Research Group. JAMA, 277(4), 325–332.https://doi.org/10.1001/jama.277.4.325
[iii] Tomita, K., Tamiya, G., Ando, S., Kitamura, N., Koizumi, H., Kato, S., Horie, Y., Kaneko, T., Azuma, T., Nagata, H., Ishii, H., & Hibi, T. (2005). AICAR, an AMPK activator, has protective effects on alcohol-induced fatty liver in rats. Alcoholism, clinical and experimental research, 29(12 Suppl), 240S–5S. https://doi.org/10.1097/01.alc.0000191126.11479.69 [iv] de Laat, M. A., Robinson, M. A., Gruntmeir, K. J., Liu, Y., Soma, L. R., & Lacombe, V. A. (2015). AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle. Veterinary journal (London, England: 1997), 205(3), 381–386. https://doi.org/10.1016/j.tvjl.2015.05.018 [v] Cuthbertson, D. J., Babraj, J. A., Mustard, K. J., Towler, M. C., Green, K. A., Wackerhage, H., Leese, G. P., Baar, K., Thomason-Hughes, M., Sutherland, C., Hardie, D. G., & Rennie, M. J. (2007). 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes, 56(8), 2078–2084. https://doi.org/10.2337/db06-1716 [vi] Višnjić D, Lalić H, Dembitz V, Tomić B, Smoljo T. AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review. Cells. 2021 May 4;10(5):1095. doi: 10.3390/cells10051095. PMID: 34064363; PMCID: PMC8147799. [vii] Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y. X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., Kang, H., Shaw, R. J., & Evans, R. M. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell, 134(3), 405–415. https://doi.org/10.1016/j.cell.2008.06.051 [viii] Goodyear, L. J. (2008). The exercise pill—too good to be true?. New England Journal of Medicine, 359(17), 1842-1844. [ix] Bueno Júnior, C. R., Pantaleão, L. C., Voltarelli, V. A., Bozi, L. H., Brum, P. C., & Zatz, M. (2012). Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance. PloS one, 7(9), e45699. https://doi.org/10.1371/journal.pone.0045699 [x] Bosselaar, M., Boon, H., van Loon, L. J., van den Broek, P. H., Smits, P., & Tack, C. J. (2009). Intra-arterial AICA-riboside administration induces NO-dependent vasodilation in vivo in human skeletal muscle. American journal of physiology. Endocrinology and metabolism, 297(3), E759–E766. https://doi.org/10.1152/ajpendo.00141.2009