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Study · Animal study (in vivo) · mouse · 2024

8 results

Administration of AICAR, an AMPK Activator, Prevents and Reverses Diabetic Polyneuropathy (DPN) by Regulating Mitophagy.

Chandrasekaran K, Choi J, Salimian M, Hedayat AF, Russell JW

International journal of molecular sciences25 Dec 2024Cited by 18 (Europe PMC)

PMID39795939 (opens in a new tab)PMCIDPMC11720447 (opens in a new tab)DOI10.3390/ijms26010080 (opens in a new tab)PepBankPUB-39795939
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Summary

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes in both Type 1 (T1D) and Type 2 (T2D). While there are no specific medications to prevent or treat DPN, certain strategies can help halt its progression. In T1D, maintaining tight glycemic control through insulin therapy can effectively prevent or delay the onset of DPN. However, in T2D, overall glucose control may only have a moderate impact on DPN, although exercise is clearly beneficial. Unfortunately, optimal exercise may not be feasible for many patients with DPN because of neuropathic foot pain and poor balance. Exercise has several favorable effects on health parameters, including body weight, glycemic control, lipid profile, and blood pressure. We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN. AICAR treatment prevented or reversed experimental DPN in mouse models of both T2D and T1D. AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001). Phospho AMP increased the levels of dynamin-related protein 1 (DRP1, a mitochondrial fission marker), increased phosphorylated autophagy activating kinase 1 (ULK1) at Serine-555, and increased microtubule-associated protein light chain 3-II (LC3-II, a marker for autophagosome assembly) by 2-fold. Mitochondria isolated from DRG neurons of HFD-fed had a decrease in ADP-stimulated state 3 respiration (120 ± 20 nmol O2/min in HFD vs. 220 ± 20 nmol O2/min in control diet (CD); p < 0.001. Mitochondria isolated from HFD+AICAR-treated mice had increased state 3 respiration (240 ± 30 nmol O2/min in HFD+AICAR). However, AICAR's protection in DPN in T2D mice was also mediated by its effects on insulin sensitivity, glucose metabolism, and lipid metabolism. Drugs that enhance AMPK phosphorylation may be beneficial in the treatment of DPN.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study8

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In mouse models of both diabetes types, AICAR prevented or reversed experimental diabetic peripheral neuropathy.

    In plain wordsIn mice with either diabetes type, AICAR prevented or reversed diabetic nerve damage.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseExperimental diabetic peripheral neuropathy
    Study

    mousen: not reported in source

    Mouse models of type 1 and type 2 diabetes
    Outcome group
    Neuroprotection · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR treatment prevented or reversed experimental DPN in mouse models of both T2D and T1D.
    1 context sentence
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In high-fat diet-fed mice, AICAR increased AMPK phosphorylation in dorsal root ganglion neuronal extracts.

    In plain wordsIn mice fed a high-fat diet, AICAR increased AMPK phosphorylation in sensory nerve cells.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAMPK phosphorylation
    Study

    mousen: not reported in source

    High-fat diet-fed mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001).
    1 context sentence
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In high-fat diet-fed mice, AICAR increased the phosphorylated-to-total AMPK ratio threefold versus high-fat diet alone.

    In plain wordsIn mice fed a high-fat diet, AICAR increased the phosphorylated-to-total AMPK ratio compared with diet alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreasePhosphorylated-to-total AMPK ratio
    Study

    mousen: not reported in source

    High-fat diet-fed mice
    Comparator
    High-fat diet without AICAR
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    Phosphorylated-to-total AMPK ratio increase
    3 fold
    HFD+AICAR versus HFD

    Source sentences

    Summary
    AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001).
    1 context sentence
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In the AICAR study, phospho AMP increased DRP1 levels, a mitochondrial fission marker.

    In plain wordsIn mice, the AICAR study reported that phospho AMP increased DRP1, a marker of mitochondrial division.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseDRP1 level
    Study

    mousen: not reported in source

    High-fat diet-fed mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Phospho AMP increased the levels of dynamin-related protein 1 (DRP1, a mitochondrial fission marker), increased phosphorylated autophagy activating kinase 1 (ULK1) at Serine-555, and increased microtubule-associated protein light chain 3-II (LC3-II, a marker for autophagosome assembly) by 2-fold.
    2 context sentences
    Summary · context
    AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001).
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In the AICAR study, phospho AMP increased ULK1 phosphorylation at Serine-555.

    In plain wordsIn mice, the AICAR study reported that phospho AMP increased ULK1 phosphorylation at Serine-555.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseULK1 phosphorylation at Serine-555
    Study

    mousen: not reported in source

    High-fat diet-fed mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Phospho AMP increased the levels of dynamin-related protein 1 (DRP1, a mitochondrial fission marker), increased phosphorylated autophagy activating kinase 1 (ULK1) at Serine-555, and increased microtubule-associated protein light chain 3-II (LC3-II, a marker for autophagosome assembly) by 2-fold.
    2 context sentences
    Summary · context
    AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001).
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In the AICAR study, phospho AMP increased LC3-II levels twofold.

    In plain wordsIn mice, the AICAR study reported that phospho AMP increased LC3-II levels.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseLC3-II level
    Study

    mousen: not reported in source

    High-fat diet-fed mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    LC3-II increase
    2 fold
    Phospho AMP result in AICAR study

    Source sentences

    Summary
    Phospho AMP increased the levels of dynamin-related protein 1 (DRP1, a mitochondrial fission marker), increased phosphorylated autophagy activating kinase 1 (ULK1) at Serine-555, and increased microtubule-associated protein light chain 3-II (LC3-II, a marker for autophagosome assembly) by 2-fold.
    2 context sentences
    Summary · context
    AICAR in high-fat diet (HFD-fed) mice increased the phosphorylation of AMPK in DRG neuronal extracts, and the ratio of phosphorylated AMPK to total AMPK increased by 3-fold (HFD vs. HFD+AICAR; p < 0.001).
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In high-fat diet-fed mice, AICAR increased neuronal mitochondrial state 3 respiration to 240 ± 30 nmol oxygen/min.

    In plain wordsIn mice fed a high-fat diet, AICAR increased oxygen use by sensory nerve cell mitochondria compared with diet alone.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseADP-stimulated state 3 respiration
    Study

    mousen: not reported in source

    High-fat diet-fed mice
    Comparator
    High-fat diet without AICAR
    Outcome group
    Mitochondrial function · Nervous system and cognition
    Studied dose
    Dose not stated

    Measurements

    State 3 respiration
    240 nmol O2/min
    HFD+AICAR
    State 3 respiration
    120 nmol O2/min
    HFD

    Source sentences

    Summary
    Mitochondria isolated from HFD+AICAR-treated mice had increased state 3 respiration (240 ± 30 nmol O2/min in HFD+AICAR).
    2 context sentences
    Summary · context
    Mitochondria isolated from DRG neurons of HFD-fed had a decrease in ADP-stimulated state 3 respiration (120 ± 20 nmol O2/min in HFD vs. 220 ± 20 nmol O2/min in control diet (CD); p < 0.001.
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.
  8. 08AnimalAnimal study (in vivo)Mechanism

    In type 2 diabetic mice, AICAR's neuropathy protection involved effects on insulin sensitivity, glucose metabolism, and lipid metabolism, without specified directions.

    In plain wordsIn diabetic mice, AICAR's nerve protection involved insulin sensitivity, glucose metabolism, and lipid metabolism. The abstract does not specify directions.

    Peptide
    AICAR (acadesine)
    Outcome
    Direction not reportedMetabolic contribution to neuropathy protection
    Study

    mousen: not reported in source

    Type 2 diabetes mice
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, AICAR's protection in DPN in T2D mice was also mediated by its effects on insulin sensitivity, glucose metabolism, and lipid metabolism.
    1 context sentence
    Summary · context
    We investigated the impact of an exercise mimetic, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), on DPN.

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.

  1. Version 2Current

    21 Oct 2026, 15:58 UTC

    Study results updated

  2. 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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