What Athletes Should Know About AICAR and Others
AICAr induces hypoglycemia in vivo 42,43 and the effect is abolished in mice lacking AMPK 32,33,35, suggesting that the effect can be more ascribed to AMPK-dependent entry of glucose than to AMPK-independent effects of AICAr on the inhibition of gluconeogenesis. In addition, AICAr may help to reduce peripheral resistance to insulin action because AICAr acts to reduce the storage of fatty acids in adipose tissue 37. In various animal models of insulin resistance, AICAr administration has been shown to improve metabolic disturbances and to enhance insulin sensitivity in peripheral tissues 44,45,46,47.
- During the course of characterizing the phenotypes of MSKO mice, Schug et al reported a similar mouse model of myeloid SIRT1 deletion 20.
- AICAr-mediated activation of mTORC2 did not result from AMPK-mediated suppression of mTORC1, and thus, reduced negative feedback on phosphatidylinositol 3-kinase (PI3K) flux, but rather on direct phosphorylation of mTOR in complex with rictor and phosphorylated Akt as a downstream target 78.
- Acadesine is added to K562 cell lines or primary cells (103 CD34+ cells/mL) growing in semisolid methyl cellulose medium.
Novel target genes in lateral entorhinal cortex
Our data suggest that an interference with NFκB DNA binding explains a unexpectedly potent and broad anti-inflammatory action of AICAR in human macrophages. Our data contrast previous observations in murine macrophages linking inhibition of inflammatory responses by ACIAR to AMPK-dependent activation of the protein deacetylase Sirt121. At the same time we corroborate findings of AMPK-independent anti-inflammatory effects in murine macrophage cell lines23,24.
4. AICAR Exhibits Synergistic Effect with Docetaxel Treatment
Joohun Ha and colleagues at Kyung Hee University, Seoul, have reviewed the research into agents designed to activate AMPK to assess their feasibility as drugs. The researchers suggest that AMPK activators are potentially useful for the treatment of conditions such as obesity, type 2 diabetes and cancer. Combining different AMPK activators in different clinical contexts might provide optimal treatment. They conclude that more research is needed to determine the precise mechanisms of action of AMPK activators and thereby optimize treatment strategies. Over the last 25 years, AICAr has been used in hundreds of studies as an activator of AMPK. The results of these initial studies pointed to the important roles of AMPK, and many of them have been later confirmed by studies in transgenic mice or by using models of cells with overexpression or down-regulation of AMPK.
Alexa Fluor® 488 Annexin V/Dead Cell Apoptosis Kit was purchased from Thermo Fisher Scientific (Waltham, MA, USA). For western blotting, rabbit antibodies against human phospho-AMPK, AMPK, MYC, mTOR, PARP, phospho-p70S6K, p70S6K, TSC-1, TSC-2, β-actin and secondary antibodies were purchased from Cell Signaling (Farmingdale, NY, USA). Mouse antibodies against human N-cadherin and E-cadherin were purchased from BD Biosciences (San Jose, CA, USA). The anti-cancer potential of AICAR has spurred extensive research into its use as a therapeutic agent.
Its ability to increase endurance by promoting energy production allows athletes to train harder and longer. This has made it a topic of interest in peptide clinics and among sports performance specialists. Unlike SARMs, which primarily target androgen receptors to promote muscle growth, Aicar directly activates AMPK, leading to different metabolic effects. Flag-PPARδ or Flag-PGC1α was immuno-precipitated from cell lysates with Anti-Flag conjugated agarose beads (Sigma). For metabolic labeling, transfected AD 293 cells were treated with p32 for 2 hr before immunoprecipitation. RNA was extracted from gastrocnemius or quadriceps using Trizol and analyzed for gene expression using real time quantitative PCR.
The antifolate pemetrexed inhibits the folate-dependent enzyme in de novo purine biosynthesis, increases ZMP, and activates AMPK 106. Methotrexate, a well-known cytostatic drug, inhibits purine de novo synthesis and potentiates the ability of exogenous AICAr to increase the level of ZMP by inhibiting AICART (Figure 3). Consequently, methotrexate enhances the ability of AICAr to activate AMPK and to inhibit the growth of human cancer cell lines 107, and promote glucose uptake and lipid oxidation in skeletal muscle 108. EMSA experiments suggest a direct interference of AICAR with NFκB DNA binding and thus, NFκB-dependent transcriptional activation. Our data confirm previous reports showing that AICAR, when incubated with nuclear extracts from murine macrophages, directly interferes with DNA binding of NFκB, CREB and C/EBPβ24.
By activating AMPK, AICAR improves insulin sensitivity, leading to enhanced glucose uptake in muscle cells and https://colompack.co/2025/01/29/understanding-steroids-uses-risks-and-guidelines-2/ other tissues. This effect has significant implications for understanding the mechanisms underlying insulin resistance and developing potential treatments for diabetes. AICAR (5-aminoimidazole-4-carboxamide ribonucleoside), also known as acadesine, is a powerful AMP-kinase activator extensively used in animal research to explore energy homeostasis and metabolic regulation.
