Effects of intravenous AICAR (5-aminoimidazole-4-carboximide riboside) administration on insulin signaling and resistance in premature baboons, Papio sp.

Blanco CL, Gastaldelli A, Anzueto DG, Winter LA, Seidner SR, McCurnin DC, Liang H, Javors MA, DeFronzo RA, Musi N

PloS one12 Dec 2018Cited by 2 (Europe PMC)

PMID30540820PMCIDPMC6291136DOI10.1371/journal.pone.0208757PepBankPUB-30540820

Summary

Premature baboons exhibit peripheral insulin resistance and impaired insulin signaling. 5' AMP-activated protein kinase (AMPK) activation improves insulin sensitivity by enhancing glucose uptake (via increased glucose transporter type 4 [GLUT4] translocation and activation of the extracellular signal-regulated kinase [ERK]/ atypical protein kinase C [aPKC] pathway), and increasing fatty acid oxidation (via inhibition of acetyl-CoA carboxylase 1 [ACC]), while downregulating gluconeogenesis (via induction of small heterodimer partner [SHP] and subsequent downregulation of the gluconeogenic enzymes: phosphoenolpyruvate carboxykinase [PEPCK], glucose 6-phosphatase [G6PASE], fructose- 1,6-bisphosphatase 1 [FBP1], and forkhead box protein 1 [FOXO1]). The purpose of this study was to investigate whether pharmacologic activation of AMPK with AICAR (5-aminoimidazole-4-carboximide riboside) administration improves peripheral insulin sensitivity in preterm baboons. 11 baboons were delivered prematurely at 125±2 days (67%) gestation. 5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1. 6 animals were in the placebo group. Euglycemic hyperinsulinemic clamps were performed at 5±2 and 14±2 days of life. Key molecules potentially altered by AICAR (AMPK, GLUT4, ACC, PEPCK, G6PASE, FBP1, and FOXO1), and the insulin signaling molecules: insulin receptor (INSR), insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were measured using RT-PCR and western blotting. AICAR infusion did not improve whole body insulin-stimulated glucose disposal in preterm baboons (12.8±2.4 vs 12.4±2.0 mg/(kg·min), p = 0.8, placebo vs AICAR). One animal developed complications during treatment. In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α). In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion. This study provides evidence that AICAR does not improve insulin sensitivity in premature euglycemic baboons, and may have adverse effects.

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

Results from this study16

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

01AnimalAnimal study (in vivo)Efficacy outcome
In premature baboons, AICAR did not improve whole-body insulin-stimulated glucose disposal versus placebo.
In plain wordsIn baboons born prematurely, AICAR did not improve insulin-stimulated glucose disposal compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeInsulin-stimulated glucose disposal
Study
baboonn = 11
Premature baboons
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Measurements
Glucose disposal
12.8 mg/(kg·min)
placebo
Glucose disposal
12.4 mg/(kg·min)
AICAR
p value
0.8
AICAR versus placebo
Source sentences
Summary
AICAR infusion did not improve whole body insulin-stimulated glucose disposal in preterm baboons (12.8±2.4 vs 12.4±2.0 mg/(kg·min), p = 0.8, placebo vs AICAR).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082001
02AnimalAnimal study (in vivo)Safety outcome
In premature baboons, one animal developed complications during AICAR treatment.
In plain wordsIn baboons born prematurely, one animal developed complications during AICAR treatment.
Peptide
AICAR (acadesine)
Outcome
Direction not reportedTreatment complications
Study
baboonn: not reported in source
Premature baboons
Outcome group
Adverse events · Whole body
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Measurements
Animals with complications
1 animal
during treatment
Source sentences
Summary
One animal developed complications during treatment.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082002
03AnimalAnimal study (in vivo)Mechanism
In premature baboon skeletal muscle, AICAR did not increase ACC phosphorylation.
In plain wordsIn baboons born prematurely, AICAR did not increase muscle ACC phosphorylation compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeMuscle ACC phosphorylation
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082003
04AnimalAnimal study (in vivo)Mechanism
In premature baboon skeletal muscle, AICAR did not increase AKT phosphorylation.
In plain wordsIn baboons born prematurely, AICAR did not increase muscle AKT phosphorylation compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeMuscle AKT phosphorylation
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082004
05AnimalAnimal study (in vivo)Mechanism
In premature baboon skeletal muscle, AICAR did not increase AMPK phosphorylation.
In plain wordsIn baboons born prematurely, AICAR did not increase muscle AMPK phosphorylation compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeMuscle AMPK phosphorylation
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082005
06AnimalAnimal study (in vivo)Mechanism
In premature baboon skeletal muscle, AICAR increased ACACA mRNA expression.
In plain wordsIn baboons born prematurely, AICAR increased muscle ACACA gene expression compared with placebo.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle ACACA mRNA
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082006
07AnimalAnimal study (in vivo)Mechanism
In premature baboon skeletal muscle, AICAR increased AKT mRNA expression.
In plain wordsIn baboons born prematurely, AICAR increased muscle AKT gene expression compared with placebo.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle AKT mRNA
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082007
08AnimalAnimal study (in vivo)Mechanism
In premature baboon skeletal muscle, AICAR increased PPARGC1A mRNA expression.
In plain wordsIn baboons born prematurely, AICAR increased muscle PPARGC1A gene expression compared with placebo.
Peptide
AICAR (acadesine)
Outcome
IncreaseMuscle PPARGC1A mRNA
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Metabolic and weight
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In skeletal muscle, AICAR infusion did not increase phosphorylation of ACC, AKT, or AMPK whereas it increased mRNA expression of ACACA (ACC), AKT, and PPARGC1A (PGC1α).
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082008
09AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, INSR was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver INSR did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver INSR
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082009
10AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, IRS1 was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver IRS1 did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver IRS1
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082010
11AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, G6PC3 was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver G6PC3 did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver G6PC3
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082011
12AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, AKT was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver AKT did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver AKT
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082012
13AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, PCK1 was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver PCK1 did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver PCK1
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082013
14AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, FOXO1 was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver FOXO1 did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver FOXO1
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082014
15AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, FBP1 was unchanged after AICAR infusion.
In plain wordsIn baboons born prematurely, liver FBP1 did not change after AICAR compared with placebo.
Peptide
AICAR (acadesine)
Outcome
No significant changeLiver FBP1
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082015
16AnimalAnimal study (in vivo)Mechanism
In premature baboon liver, AICAR increased PPARGC1A mRNA expression.
In plain wordsIn baboons born prematurely, AICAR increased liver PPARGC1A gene expression compared with placebo.
Peptide
AICAR (acadesine)
Outcome
IncreaseLiver PPARGC1A mRNA
Study
baboonn: not reported in source
Premature baboons
Comparator
Placebo
Outcome group
Receptor activity and mechanism · Liver
Studied dose
0.5 mg·g-1·day-1 · intravenous infusion · 5 daysAs given in this study (baboon).
Source sentences
Summary
In the liver, INSR, IRS1, G6PC3, AKT, PCK1, FOXO1, and FBP1 were unchanged, whereas PPARGC1A mRNA expression increased after AICAR infusion.
3 context sentences(design, population, supporting numbers)
Summary · context
11 baboons were delivered prematurely at 125±2 days (67%) gestation.
Summary · context
5 animals were randomized to receive 5 days of continuous AICAR infusion at a dose of 0.5 mg·g-1·day-1.
Summary · context
6 animals were in the placebo group.
Show in the study text Report a problemFND-3054082016

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

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Effects of intravenous AICAR (5-aminoimidazole-4-carboximide riboside) administration on insulin signaling and resistance in premature baboons, Papio sp.

Summary

Results from this study16

Version history

Subjects

Publication types

MeSH terms