Chronic treatment with the AMP-kinase activator AICAR increases glycogen storage and fatty acid oxidation in skeletal muscles but does not reduce hyperglucagonemia and hyperglycemia in insulin deficient rats.

Vitzel KF, Bikopoulos G, Hung S, Pistor KE, Patterson JD, Curi R, Ceddia RB

PloS one19 Apr 2013Cited by 20 (Europe PMC)

PMID23620811PMCIDPMC3631222DOI10.1371/journal.pone.0062190PepBankPUB-23620811

Summary

This study tested whether the glycogen-accumulating effect of chronic in vivo pharmacological 5'AMP-activated protein kinase (AMPK) activation could improve glycemic control under conditions of insulin deficiency. Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR). Subsequently, glycogen content and synthesis, glucose oxidation, and fatty acid oxidation (FAO) were determined in oxidative and glycolytic skeletal muscles. Glycemia, insulinemia, glucagonemia, and circulating triglycerides (TG) and non-esterified fatty acids (NEFAs) were measured after AICAR treatment. Insulin was almost undetectable in STZ rats and these animals were severely hyperglycemic. Glycogen content was markedly low mainly in glycolytic muscles of STZ rats and AICAR treatment restored it to control values. No differences were found among all muscles studied with regards to the content and phosphorylation of Akt/protein kinase B and glycogen synthase kinase 3. Even though glycogen synthase content was reduced in all muscles from STZ rats, insulin-induced dephosphorylation/activation of this enzyme was preserved and unaffected by AICAR treatment. Glucagon and NEFAS were 2- and 7.4-fold fold higher in STZ rats than controls, respectively. AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles. In conclusion, even though AICAR-induced AMPK activation enhanced glycogen accumulation in glycolytic muscles and normalized circulating NEFAs and TG levels, the hyperglycemic effects of glucagon likely offset the potentially glucose-lowering effects of AICAR, resulting in no improvement of glycemic control in insulin-deficient rats.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In STZ rats, AICAR restored depleted muscle glycogen content to control values, mainly in glycolytic muscles.
In plain wordsIn rats with insulin deficiency, AICAR restored muscle glycogen to control levels, mainly in glycolytic muscles.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle glycogen content
Study
ratn: not reported in source
STZ-induced insulin deficiency in male Wistar rats
Outcome group
Glycemic control · Musculoskeletal
Studied dose
Dose not stated · 7 consecutive daysAs given in this study (rat).
Source sentences
Summary
Glycogen content was markedly low mainly in glycolytic muscles of STZ rats and AICAR treatment restored it to control values.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR).
Show in the study text Report a problemFND-2362081101
02AnimalAnimal study (in vivo)Efficacy outcome
In STZ rats, AICAR did not affect preserved insulin-induced glycogen synthase dephosphorylation and activation.
In plain wordsIn rats with insulin deficiency, AICAR did not change insulin-induced glycogen synthase activation.
Peptide
AICAR (acadesine)
Outcome
No significant changeInsulin-induced glycogen synthase activation
Study
ratn: not reported in source
STZ-induced insulin deficiency in male Wistar rats
Outcome group
Receptor activity and mechanism · Musculoskeletal
Studied dose
Dose not stated · 7 consecutive daysAs given in this study (rat).
Source sentences
Summary
Even though glycogen synthase content was reduced in all muscles from STZ rats, insulin-induced dephosphorylation/activation of this enzyme was preserved and unaffected by AICAR treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR).
Show in the study text Report a problemFND-2362081102
03AnimalAnimal study (in vivo)Efficacy outcome
In STZ rats, AICAR did not affect hyperglycemia.
In plain wordsIn rats with insulin deficiency, AICAR did not reduce high blood glucose.
Peptide
AICAR (acadesine)
Outcome
No significant changeHyperglycemia
Study
ratn: not reported in source
STZ-induced insulin deficiency in male Wistar rats
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 7 consecutive daysAs given in this study (rat).
Source sentences
Summary
AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR).
Show in the study text Report a problemFND-2362081103
04AnimalAnimal study (in vivo)Efficacy outcome
In STZ rats, AICAR did not affect hyperglucagonemia.
In plain wordsIn rats with insulin deficiency, AICAR did not reduce high glucagon levels.
Peptide
AICAR (acadesine)
Outcome
No significant changeHyperglucagonemia
Study
ratn: not reported in source
STZ-induced insulin deficiency in male Wistar rats
Outcome group
Hormone levels · Endocrine and hormones
Studied dose
Dose not stated · 7 consecutive daysAs given in this study (rat).
Source sentences
Summary
AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR).
Show in the study text Report a problemFND-2362081104
05AnimalAnimal study (in vivo)Efficacy outcome
In STZ rats, AICAR normalized elevated circulating non-esterified fatty acids.
In plain wordsIn rats with insulin deficiency, AICAR restored high circulating fatty acid levels to normal.
Peptide
AICAR (acadesine)
Outcome
DecreaseCirculating NEFAs
Study
ratn: not reported in source
STZ-induced insulin deficiency in male Wistar rats
Outcome group
Lipids · Metabolic and weight
Studied dose
Dose not stated · 7 consecutive daysAs given in this study (rat).
Source sentences
Summary
AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles.
2 context sentences(design, population, supporting numbers)
Summary · context
Glucagon and NEFAS were 2- and 7.4-fold fold higher in STZ rats than controls, respectively.
Summary · context
Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR).
Show in the study text Report a problemFND-2362081105
06AnimalAnimal study (in vivo)Efficacy outcome
In STZ rats, AICAR significantly increased fatty acid oxidation in glycolytic muscles.
In plain wordsIn rats with insulin deficiency, AICAR increased fatty acid oxidation in glycolytic muscles.
Peptide
AICAR (acadesine)
Outcome
IncreaseGlycolytic muscle fatty acid oxidation
Study
ratn: not reported in source
STZ-induced insulin deficiency in male Wistar rats
Outcome group
Lipids · Musculoskeletal
Studied dose
Dose not stated · 7 consecutive daysAs given in this study (rat).
Source sentences
Summary
AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles.
1 context sentence(design, population, supporting numbers)
Summary · context
Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR).
Show in the study text Report a problemFND-2362081106

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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