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Study · Animal study (in vivo) · mouse · 2016

9 results

Exendin-4 attenuates adverse cardiac remodelling in streptozocin-induced diabetes via specific actions on infiltrating macrophages.

Tate M, Robinson E, Green BD, McDermott BJ, Grieve DJ

Basic research in cardiology23 Nov 2015Cited by 55 (Europe PMC)

PMID26597728 (opens in a new tab)PMCIDPMC4656717 (opens in a new tab)DOI10.1007/s00395-015-0518-1 (opens in a new tab)PepBankPUB-26597728
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Summary

In addition to its' established metabolic and cardioprotective effects, glucagon-like peptide-1 (GLP-1) reduces post-infarction heart failure via preferential actions on the extracellular matrix (ECM). Here, we investigated whether the GLP-1 mimetic, exendin-4, modulates cardiac remodelling in experimental diabetes by specifically targeting inflammatory/ECM pathways, which are characteristically dysregulated in this setting. Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks. Exendin-4 and insulin improved metabolic parameters in diabetic mice after 12 weeks, but only exendin-4 reduced cardiac diastolic dysfunction and interstitial fibrosis in parallel with altered ECM gene expression. Whilst myocardial inflammation was not evident at 12 weeks, CD11b-F4/80(++) macrophage infiltration at 4 weeks was increased and reduced by exendin-4, together with an improved cytokine profile. Notably, media collected from high glucose-treated macrophages induced cardiac fibroblast differentiation, which was prevented by exendin-4, whilst several cytokines/chemokines were differentially expressed/secreted by exendin-4-treated macrophages, some of which were modulated in STZ exendin-4-treated hearts. Our findings suggest that exendin-4 preferentially protects against ECM remodelling and diastolic dysfunction in experimental diabetes via glucose-dependent modulation of paracrine communication between infiltrating macrophages and resident fibroblasts, thereby indicating that cell-specific targeting of GLP-1 signalling may be a viable therapeutic strategy in this setting.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

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

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    In diabetic mice, exendin‑4 improved unspecified metabolic parameters after 12 weeks.

    In plain wordsIn mice with diabetes, exendin‑4 improved metabolic measures after 12 weeks.

    Peptide
    Exenatide (exendin-4)
    Outcome
    MixedMetabolic parameters
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated · 12 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Exendin-4 and insulin improved metabolic parameters in diabetic mice after 12 weeks, but only exendin-4 reduced cardiac diastolic dysfunction and interstitial fibrosis in parallel with altered ECM gene expression.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In diabetic mice, exendin‑4 reduced cardiac diastolic dysfunction after 12 weeks, whereas insulin did not.

    In plain wordsIn mice with diabetes, exendin‑4 reduced impaired heart relaxation after 12 weeks, whereas insulin did not.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac diastolic dysfunction
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · 12 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Exendin-4 and insulin improved metabolic parameters in diabetic mice after 12 weeks, but only exendin-4 reduced cardiac diastolic dysfunction and interstitial fibrosis in parallel with altered ECM gene expression.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In diabetic mice, exendin‑4 reduced interstitial fibrosis after 12 weeks, whereas insulin did not.

    In plain wordsIn mice with diabetes, exendin‑4 reduced heart tissue fibrosis after 12 weeks, whereas insulin did not.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseInterstitial fibrosis
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated · 12 weeksAs given in this study (mouse).

    Source sentences

    Summary
    Exendin-4 and insulin improved metabolic parameters in diabetic mice after 12 weeks, but only exendin-4 reduced cardiac diastolic dysfunction and interstitial fibrosis in parallel with altered ECM gene expression.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  4. 04AnimalAnimal study (in vivo)Mechanism

    In diabetic mice, exendin‑4 altered extracellular matrix gene expression.

    In plain wordsIn mice with diabetes, exendin‑4 changed extracellular matrix gene expression.

    Peptide
    Exenatide (exendin-4)
    Outcome
    MixedECM gene expression
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Receptor activity and mechanism · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Exendin-4 and insulin improved metabolic parameters in diabetic mice after 12 weeks, but only exendin-4 reduced cardiac diastolic dysfunction and interstitial fibrosis in parallel with altered ECM gene expression.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In diabetic mice, exendin‑4 reduced elevated cardiac macrophage infiltration at 4 weeks.

    In plain wordsIn mice with diabetes, exendin‑4 reduced heart macrophage infiltration at 4 weeks.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseMacrophage infiltration
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Whilst myocardial inflammation was not evident at 12 weeks, CD11b-F4/80(++) macrophage infiltration at 4 weeks was increased and reduced by exendin-4, together with an improved cytokine profile.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  6. 06AnimalAnimal study (in vivo)Mechanism

    In diabetic mice, exendin‑4 improved the cytokine profile at 4 weeks.

    In plain wordsIn mice with diabetes, exendin‑4 improved the cytokine profile at 4 weeks.

    Peptide
    Exenatide (exendin-4)
    Outcome
    MixedCytokine profile
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Whilst myocardial inflammation was not evident at 12 weeks, CD11b-F4/80(++) macrophage infiltration at 4 weeks was increased and reduced by exendin-4, together with an improved cytokine profile.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  7. 07AnimalAnimal study (in vivo)Mechanism

    In diabetic mice, exendin‑4 modulated some cytokines or chemokines also affected in treated macrophages.

    In plain wordsIn mice with diabetes, exendin‑4 changed some heart cytokines or chemokines also affected in treated macrophages.

    Peptide
    Exenatide (exendin-4)
    Outcome
    MixedCardiac cytokine and chemokine modulation
    Study

    mousen: not reported in source

    streptozotocin-induced diabetes
    Outcome group
    Inflammation markers · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    whilst several cytokines/chemokines were differentially expressed/secreted by exendin-4-treated macrophages, some of which were modulated in STZ exendin-4-treated hearts.
    1 context sentence
    Summary · context
    Adult mice were subjected to streptozotocin (STZ) diabetes and infused with exendin-4/insulin/saline from 0 to 4 or 4-12 weeks.
  8. 08LabIn vitro (cells)Mechanism

    In cell experiments, exendin‑4 prevented cardiac fibroblast differentiation induced by media from high glucose-treated macrophages.

    In plain wordsIn cells, exendin‑4 prevented heart fibroblast differentiation induced by media from macrophages exposed to high glucose.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseCardiac fibroblast differentiation
    Study

    n: not reported in source

    high glucose-treated macrophages and cardiac fibroblasts
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Notably, media collected from high glucose-treated macrophages induced cardiac fibroblast differentiation, which was prevented by exendin-4
  9. 09LabIn vitro (cells)Mechanism

    In macrophages, exendin‑4 altered expression or secretion of unspecified cytokines and chemokines.

    In plain wordsIn cells, exendin‑4 changed cytokine and chemokine production or release by macrophages.

    Peptide
    Exenatide (exendin-4)
    Outcome
    MixedCytokine and chemokine expression and secretion
    Study

    n: not reported in source

    high glucose-treated macrophages
    Outcome group
    Inflammation markers · Immune and inflammation
    Studied dose
    Dose not stated

    Source sentences

    Summary
    whilst several cytokines/chemokines were differentially expressed/secreted by exendin-4-treated macrophages, some of which were modulated in STZ exendin-4-treated hearts.

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

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