AICAR

AICAR, aminoimidazole carboxamide ribonucleotide, acts as an agonist to AMP-activated protein kinase; AMP-activated protein kinase, also known as AMPK, is an enzyme with an important role in cellular homeostasis and energy regulation. AMPK acts through a variety of means to ultimately stimulate liver fatty oxidation, ketogenesis, beta-cell modulation of insulin secretion, and other functions within the body.  AICAR has been shown to stimulate glucose uptake and reduce apoptosis by reducing reactive oxygen compounds within cells.

In a breakthrough study in 2008, Narkar et al of the Salk Institute discovered that AICAR significantly improves the performance of mice in endurance-type exercise by converting fast-twitch muscle fibers to the more energy-efficient, fat-burning, slow-twitch type. They also found that AICAR and GW1516, when given to “sedentary” mice, activated 40% of the genes that were turned on when mice were given GW1516 and made to exercise. As a result a publicity storm about “exercise pills” and “exercise in a pill” ensued.  The World Anti-Doping Agency now lists both compounds on their prohibited list (since 2009), and the lead researcher of the breakthrough study cooperated in providing data to make possible a urinalysis test to detect AICAR.

AICAR has a number of other experimental/clinical and research chemical uses as it is expressed in a variety of tissue types.  Bai et al found that “data demonstrate that AICAR-initiated AMPK activation may represent a promising alternative to our current approaches to suppressing intestinal inflammation in IBD.”

Guo et al found “results suggest[ing] a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers.”

An original study by Pold et al offers additional hope that AICAR could offer important treatment potential for humans:

Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.