AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.

@article{Merrill1997AICARI,
  title={AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.},
  author={Gary F. Merrill and E J Kurth and David Grahame Hardie and William W. Winder},
  journal={American journal of physiology. Endocrinology and metabolism},
  year={1997},
  volume={273 6},
  pages={E1107-E1112}
}
  • G. Merrill, E. Kurth, W. Winder
  • Published 1 December 1997
  • Biology, Computer Science
  • American journal of physiology. Endocrinology and metabolism
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum… 
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AMP kinase activation with AICAR simultaneously increases fatty acid and glucose oxidation in resting rat soleus muscle
TLDR
AMPK appears to be an important regulator of both FA metabolism and glucose oxidation in resting skeletal muscle.
AMP kinase activation with AICAR further increases fatty acid oxidation and blunts triacylglycerol hydrolysis in contracting rat soleus muscle
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Results suggest that FA metabolism is very sensitive to AMPK α2 stimulation during contraction, suggesting a better matching between TAG hydrolysis and subsequent oxidative needs of the muscle.
Regulation of fatty acid oxidation and glucose metabolism in rat soleus muscle: effects of AICAR.
TLDR
The results indicate that, in incubated rat soleus muscle, AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, and the ability of AICARS to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat.
Influence of malonyl-CoA and palmitate concentration on rate of palmitate oxidation in rat muscle.
TLDR
Results provide additional evidence that malonyl-CoA is an important regulator of the rate of fatty acid oxidation at palmitate concentrations in the physiological range.
Isoproterenol stimulates 5'-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts.
TLDR
The hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation is tested, and data suggest net rates of acetyl-CoA utilization exceed the net ratesof acetyl -CoA generation is suggested.
Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle.
TLDR
Chronic chemical activation of AMPK results in increases in GLUT-4 protein, hexokinase activity, and glycogen, similarly to those induced by endurance training.
AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo.
TLDR
It is concluded that both glucose and FA fluxes are enhanced by AICAR more in white versus red muscle, consistent with the relative degree of activation of AMPK.
AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle.
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Evidence is provided that AMPK signaling is linked to the transcriptional regulation of select metabolic genes in skeletal muscle by a single-leg arterial infusion technique employed in fully conscious rats.
Glycogen-dependent effects of 5-aminoimidazole-4-carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle.
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It is concluded that acute AICA-riboside treatment leads to phosphorylation and deactivation of glycogen synthase in skeletal muscle and may be a target for AMPK in vivo.
Insulin stimulation of glucose uptake fails to decrease palmitate oxidation in muscle if AMPK is activated.
TLDR
It is concluded that AMPK activation can prevent high rates of glucose uptake and glycolytic flux from inhibiting palmitate oxidation in predominantly fast-twitch muscle under these conditions.
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References

SHOWING 1-10 OF 42 REFERENCES
Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise.
TLDR
The activation of the AMP-activated protein kinase with consequent phosphorylation and inactivation of ACC may be one of the primary events in the control of malonyl-CoA and hence fatty acid oxidation during exercise.
Stimulation of rat liver AMP-activated protein kinase by AMP analogues.
Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation.
TLDR
It is concluded that malonyl-CoA can be synthesized within cardiac myocytes and that the level of this metabolite can be acutely regulated, likely to have consequences for the regulation of carnitine palmitoyltransferase in the heart.
5‐Aminoimidazole‐4‐Carboxamide Ribonucleoside
TLDR
AICAR provides direct evidence that the inhibition by AMPK of activation of hormone-sensitive lipase by cyclic-AMP-dependent protein kinase also operates in intact cells, and should be a useful tool for identifying new target pathways and processes regulated by theprotein kinase cascade.
Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart.
TLDR
It is concluded that ACC is an important regulator of fatty acid oxidation in the heart and that acetyl-CoA supply is a key determinant of heart ACC-280 activity.
Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP‐activated protein kinase
TLDR
Findings open new perspectives for the simultaneous control of triglyceride and cholesterol synthesis by pharmacological stimulators of AMP‐activated protein kinase.
Contraction-induced Changes in Acetyl-CoA Carboxylase and 5′-AMP-activated Kinase in Skeletal Muscle*
The concentration of malonyl-CoA, a negative regulator of fatty acid oxidation, diminishes acutely in contracting skeletal muscle. To determine how this occurs, the activity and properties of…
Malonyl-CoA regulation in skeletal muscle: its link to cell citrate and the glucose-fatty acid cycle.
TLDR
The results suggest that in the presence of glucose, insulin and acetoacetate acutely increase malonyl-CoA levels in the incubated soleus by increasing the cytosolic concentration of citrate, a novel mechanism that could complement the glucose-fatty acid cycle in determining how muscle chooses its fuels.
5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?
TLDR
AICAR provides direct evidence that the inhibition by AMPK of activation of hormone-sensitive lipase by cyclic-AMP-dependent protein kinase also operates in intact cells, and should be a useful tool for identifying new target pathways and processes regulated by theprotein kinase cascade.
Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A.
TLDR
Muscle ACC can be phosphorylated by PKA but with no apparent functional effects on the enzyme, and AMPK appears to be the more important regulator of muscle ACC.
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