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Study · In vitro (cells) · mouse · 2015

11 results

Insulin Resistance Prevents AMPK-induced Tau Dephosphorylation through Akt-mediated Increase in AMPKSer-485 Phosphorylation.

Kim B, Figueroa-Romero C, Pacut C, Backus C, Feldman EL

The Journal of biological chemistry22 Jun 2015Cited by 50 (Europe PMC)

PMID26100639 (opens in a new tab)PMCIDPMC4521037 (opens in a new tab)DOI10.1074/jbc.m115.636852 (opens in a new tab)PepBankPUB-26100639
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Summary

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, diabetes, and dyslipidemia, and insulin resistance (IR) is the central feature of MetS. Recent studies suggest that MetS is a risk factor for Alzheimer disease (AD). AMP-activated kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme and a key player in regulating energy metabolism. In this report, we examined the role of IR on the regulation of AMPK phosphorylation and AMPK-mediated Tau phosphorylation. We found that AMPK(Ser-485), but not AMPK(Thr-172), phosphorylation is increased in the cortex of db/db and high fat diet-fed obese mice, two mouse models of IR. In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485. AMPK activation also triggered Tau dephosphorylation. When IR was mimicked in vitro by chronically treating the cells with insulin, AICAR specifically induced AMPK(Ser-485), but not AMPK(Thr-172), hyperphosphorylation whereas AICAR-induced Tau dephosphorylation was inhibited. IR also resulted in the overactivation of Akt by AICAR treatment; however, preventing Akt overactivation during IR prevented AMPK(Ser-485) hyperphosphorylation and restored AMPK-mediated Tau dephosphorylation. Transfection of AMPK(S485A) mutant caused similar results. Therefore, our results suggest the following mechanism for the adverse effect of IR on AD pathology: IR → chronic overactivation of Akt → AMPK(Ser-485) hyperphosphorylation → inhibition of AMPK-mediated Tau dephosphorylation. Together, our results show for the first time a possible contribution of IR-induced AMPK(Ser-485) phosphorylation to the increased risk of AD in obesity and diabetes.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

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

  1. 01LabIn vitro (cells)Mechanism

    In cortical cells, AICAR induced AMPK Thr-172 phosphorylation.

    In plain wordsIn cells, AICAR increased AMPK phosphorylation at Thr-172.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAMPK Thr-172 phosphorylation
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485.
  2. 02LabIn vitro (cells)Mechanism

    In cortical cells, AICAR induced AMPK Ser-485 phosphorylation.

    In plain wordsIn cells, AICAR increased AMPK phosphorylation at Ser-485.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAMPK Ser-485 phosphorylation
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485.
  3. 03LabIn vitro (cells)Mechanism

    In cortical cells, AMPK activation by AICAR triggered Tau dephosphorylation.

    In plain wordsIn cells, AICAR-triggered AMPK activation reduced Tau phosphorylation.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseTau phosphorylation
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    AMPK activation also triggered Tau dephosphorylation.
    1 context sentence
    Summary · context
    In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485.
  4. 04LabIn vitro (cells)Mechanism

    In insulin-resistant cortical cells, AICAR induced AMPK Ser-485 hyperphosphorylation.

    In plain wordsIn cells with insulin resistance, AICAR increased AMPK Ser-485 phosphorylation excessively.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAMPK Ser-485 hyperphosphorylation during insulin resistance
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    When IR was mimicked in vitro by chronically treating the cells with insulin, AICAR specifically induced AMPK(Ser-485), but not AMPK(Thr-172), hyperphosphorylation whereas AICAR-induced Tau dephosphorylation was inhibited.
  5. 05LabIn vitro (cells)Mechanism

    In insulin-resistant cortical cells, AICAR did not induce AMPK Thr-172 hyperphosphorylation.

    In plain wordsIn cells with insulin resistance, AICAR did not cause excessive AMPK Thr-172 phosphorylation.

    Peptide
    AICAR (acadesine)
    Outcome
    No significant changeAMPK Thr-172 hyperphosphorylation during insulin resistance
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    When IR was mimicked in vitro by chronically treating the cells with insulin, AICAR specifically induced AMPK(Ser-485), but not AMPK(Thr-172), hyperphosphorylation whereas AICAR-induced Tau dephosphorylation was inhibited.
  6. 06LabIn vitro (cells)Mechanism

    In insulin-resistant cortical cells, AICAR treatment overactivated Akt.

    In plain wordsIn cells with insulin resistance, AICAR caused excessive Akt activation.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseAkt overactivation during insulin resistance
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition
    Studied dose
    Dose not stated

    Source sentences

    Summary
    IR also resulted in the overactivation of Akt by AICAR treatment

Studies that did not test the peptide alone5

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

  1. 07LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism

    In cortical cells, insulin resistance inhibited AICAR-induced Tau dephosphorylation.

    In plain wordsIn cells, insulin resistance reduced AICAR's effect on Tau dephosphorylation.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseTau dephosphorylation during insulin resistance
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition

    Source sentences

    Summary
    When IR was mimicked in vitro by chronically treating the cells with insulin, AICAR specifically induced AMPK(Ser-485), but not AMPK(Thr-172), hyperphosphorylation whereas AICAR-induced Tau dephosphorylation was inhibited.

    In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).

  2. 08LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism

    In insulin-resistant cells, prevention of Akt overactivation prevented AMPK Ser-485 hyperphosphorylation during AICAR treatment.

    In plain wordsIn cells with insulin resistance, blocking excessive Akt activity prevented excessive AMPK Ser-485 phosphorylation during AICAR treatment.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseAMPK Ser-485 response to Akt blockade
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition

    Source sentences

    Summary
    IR also resulted in the overactivation of Akt by AICAR treatment; however, preventing Akt overactivation during IR prevented AMPK(Ser-485) hyperphosphorylation and restored AMPK-mediated Tau dephosphorylation.

    In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).

  3. 09LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism

    In insulin-resistant cells, prevention of Akt overactivation restored AMPK-mediated Tau dephosphorylation during AICAR treatment.

    In plain wordsIn cells with insulin resistance, blocking excessive Akt activity restored Tau dephosphorylation during AICAR treatment.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseTau dephosphorylation after Akt blockade
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition

    Source sentences

    Summary
    IR also resulted in the overactivation of Akt by AICAR treatment; however, preventing Akt overactivation during IR prevented AMPK(Ser-485) hyperphosphorylation and restored AMPK-mediated Tau dephosphorylation.

    In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).

  4. 10LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism

    In insulin-resistant cortical cells, AMPK(S485A) mutant transfection prevented AMPK Ser-485 hyperphosphorylation, similarly to prevention of Akt overactivation.

    In plain wordsIn insulin-resistant cells, AMPK mutant transfection prevented excessive AMPK Ser-485 phosphorylation, similarly to prevention of excessive Akt activity.

    Peptide
    AICAR (acadesine)
    Outcome
    DecreaseAMPK Ser-485 hyperphosphorylation after mutant transfection
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition

    Source sentences

    Summary
    Transfection of AMPK(S485A) mutant caused similar results.
    2 context sentences
    Summary · context
    IR also resulted in the overactivation of Akt by AICAR treatment; however, preventing Akt overactivation during IR prevented AMPK(Ser-485) hyperphosphorylation and restored AMPK-mediated Tau dephosphorylation.
    Summary · context
    In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485.

    In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).

  5. 11LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism

    In insulin-resistant cortical cells, AMPK(S485A) mutant transfection restored AMPK-mediated Tau dephosphorylation, similarly to prevention of Akt overactivation.

    In plain wordsIn insulin-resistant cells, AMPK mutant transfection restored Tau dephosphorylation, similarly to prevention of excessive Akt activity.

    Peptide
    AICAR (acadesine)
    Outcome
    IncreaseTau dephosphorylation after mutant transfection
    Study

    human and mousen: not reported in source

    HK-5320 cortical stem cells and primary mouse embryonic cortical neurons
    Outcome group
    Receptor activity and mechanism · Nervous system and cognition

    Source sentences

    Summary
    Transfection of AMPK(S485A) mutant caused similar results.
    2 context sentences
    Summary · context
    IR also resulted in the overactivation of Akt by AICAR treatment; however, preventing Akt overactivation during IR prevented AMPK(Ser-485) hyperphosphorylation and restored AMPK-mediated Tau dephosphorylation.
    Summary · context
    In vitro, treatment of human cortical stem cell line (HK-5320) and primary mouse embryonic cortical neurons with the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), induced AMPK phosphorylation at both Thr-172 and Ser-485.

    In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).

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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