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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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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