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Study · Animal study (in vivo) · rat · 2019

10 results

Exendin-4 Protects against Hyperglycemia-Induced Cardiomyocyte Pyroptosis via the AMPK-TXNIP Pathway.

Wei H, Bu R, Yang Q, Jia J, Li T, Wang Q, Chen Y

Journal of diabetes research9 Dec 2019Cited by 75 (Europe PMC)

PMID31886288 (opens in a new tab)PMCIDPMC6925927 (opens in a new tab)DOI10.1155/2019/8905917 (opens in a new tab)PepBankPUB-31886288
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Summary

Diabetic cardiomyopathy is a common cardiac condition in patients with diabetes mellitus, which results in cardiac hypertrophy and subsequent heart failure. Chronic inflammation in the diabetic heart results in loss of cardiomyocytes and subsequentially cardiac dysfunction. Accumulated evidence implicated pyroptosis as a vital contributor to the hyperglycemia-induced cardiac inflammatory response. Exendin-4, a GLP analog, promotes survival of cardiomyocytes in cardiovascular diseases, including diabetic cardiomyopathy. However, the role of Exendin-4 in cardiac pyroptosis remains to be elucidated. Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats. The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well. In an effort to understand the signaling mechanisms underlying the antipyroptotic property of Exendin-4, we found that blockade of AMPK, an oxidative stress sensor, activity diminished the antipyroptotic property of Exendin-4. Phosphorylation of AMPK resulted in degeneration of TXNIP that promoted the activation of the NLRP3 inflammasome. Exendin-4 treatment decreased the protein level of TXNIP. Moreover, RNA silencing of TXNIP mimicked the antipyroptotic actions of Exendin-4. These findings promoted us to propose a new signaling pathway mediating cardioprotective effect of Exendin-4 under hyperglycemic conditions: Exendin-4 → ROS↓ → pAMPK↑ → TXNIP↓ → caspase-1↓ → IL-1β and IL-18↓ → pyroptosis↓. In general, our study identified Exendin-4 as a pyroptotic inhibitor protecting against hyperglycemia-induced cardiomyocyte pyroptosis via the AMPK-TXNIP pathway.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat diet-fed rats, exendin‑4 protected against cardiac remodeling.

    In plain wordsIn rats fed a high-fat diet, exendin‑4 protected against cardiac remodeling.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac remodeling
    Study

    ratn: not reported in source

    High-fat diet-fed diabetic rats
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In high-fat diet-fed rats, exendin‑4 protected against cardiac dysfunction.

    In plain wordsIn rats fed a high-fat diet, exendin‑4 protected against cardiac dysfunction.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac dysfunction
    Study

    ratn: not reported in source

    High-fat diet-fed diabetic rats
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats.
  3. 03AnimalAnimal study (in vivo)Mechanism

    In high-fat diet-fed rats, exendin‑4 attenuated cardiac inflammation.

    In plain wordsIn rats fed a high-fat diet, exendin‑4 reduced cardiac inflammation.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac inflammation
    Study

    ratn: not reported in source

    High-fat diet-fed diabetic rats
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In diabetic rat hearts, exendin‑4 inhibited caspase-1 activity.

    In plain wordsIn rats with diabetes, exendin‑4 reduced heart caspase-1 activity.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac caspase-1 activity
    Study

    ratn: not reported in source

    High-fat diet-fed diabetic rats
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well.
    1 context sentence
    Summary · context
    Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In diabetic rat hearts, exendin‑4 inhibited pyroptotic cytokine production.

    In plain wordsIn rats with diabetes, exendin‑4 reduced heart pyroptotic cytokine production.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac pyroptotic cytokine production
    Study

    ratn: not reported in source

    High-fat diet-fed diabetic rats
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well.
    1 context sentence
    Summary · context
    Our study revealed that Exendin-4 treatment protected against heart remolding and dysfunction and attenuated cardiac inflammation in high-fat diet-fed rats.
  6. 06LabIn vitro (cells)Mechanism

    In high glucose-treated cardiomyocytes, exendin‑4 inhibited caspase-1 activity.

    In plain wordsIn cells exposed to high glucose, exendin‑4 reduced caspase-1 activity.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCellular caspase-1 activity
    Study

    n: not reported in source

    High glucose-treated cardiomyocytes
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well.
  7. 07LabIn vitro (cells)Mechanism

    In high glucose-treated cardiomyocytes, exendin‑4 inhibited pyroptotic cytokine production.

    In plain wordsIn cells exposed to high glucose, exendin‑4 reduced pyroptotic cytokine production.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCellular pyroptotic cytokine production
    Study

    n: not reported in source

    High glucose-treated cardiomyocytes
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    The activity of caspase-1 and production of pyroptotic cytokines were significantly inhibited by Exendin-4 treatment in the diabetic heart and in high glucose-treated cardiomyocytes as well.
  8. 08LabOther designMechanism

    In the experimental cardiac models, exendin‑4 decreased TXNIP protein levels.

    In plain wordsIn lab tests, exendin‑4 decreased TXNIP protein levels.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseTXNIP protein
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Exendin-4 treatment decreased the protein level of TXNIP.

Studies that did not test the peptide alone2

In this study, Exenatide (exendin-4) 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 Exenatide (exendin-4).

  1. 09LabNot a test of Exenatide (exendin-4) aloneOther designMechanism

    In the experimental cardiac models, AMPK blockade diminished the antipyroptotic effect of exendin‑4.

    In plain wordsIn lab tests, AMPK blockade reduced the protective effect of exendin‑4 against pyroptosis.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseAMPK dependence of antipyroptotic effect
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cardiovascular

    Source sentences

    Summary
    In an effort to understand the signaling mechanisms underlying the antipyroptotic property of Exendin-4, we found that blockade of AMPK, an oxidative stress sensor, activity diminished the antipyroptotic property of Exendin-4.

    In this study, Exenatide (exendin-4) 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 Exenatide (exendin-4).

  2. 10LabNot a test of Exenatide (exendin-4) aloneOther designMechanism

    In experimental cardiac models, TXNIP RNA silencing mimicked the antipyroptotic actions of exendin‑4.

    In plain wordsIn lab tests, TXNIP gene silencing mimicked the effects of exendin‑4 against pyroptosis.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseTXNIP silencing mimics antipyroptotic actions
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Cardiovascular

    Source sentences

    Summary
    Moreover, RNA silencing of TXNIP mimicked the antipyroptotic actions of Exendin-4.

    In this study, Exenatide (exendin-4) 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 Exenatide (exendin-4).

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

    22 Oct 2026, 02:26 UTC

    Study results updated

  2. Version 1

    21 Oct 2026, 18:59 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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