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Study · Animal study (in vivo) · mouse · 2006

11 results

Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function.

Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, White MF

The Journal of biological chemistry4 Nov 2005Cited by 166 (Europe PMC)

PMID16272563 (opens in a new tab)DOI10.1074/jbc.m508307200 (opens in a new tab)PepBankPUB-16272563
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Summary

The insulin receptor substrate 2 (Irs2) branch of the insulin/insulin-like growth factor-signaling cascade prevents diabetes in mice because it promotes beta cell replication, function, and survival, especially during metabolic stress. Because exendin-4 (Ex4), a long acting glucagon-like peptide 1 receptor agonist, has similar effects upon beta cells in rodents and humans, we investigated whether Irs2 signaling was required for Ex4 action in isolated beta cells and in Irs2(-/-) mice. Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation. In wild type mice Ex4 administered continuously for 28 days increased beta cell mass 2-fold. By contrast, Ex4 failed to arrest the progressive beta cell loss in Irs2(-/-) mice, which culminated in fatal diabetes; however, Ex4 delayed the progression of diabetes by 3 weeks by promoting insulin secretion from the remaining islets. We conclude that some short term therapeutic effects of glucagon-like peptide 1 receptor agonists can be independent of Irs2, but its long term effects upon beta cell growth and survival are mediated by the Irs2 branch of the insulin/insulin-like growth factor signaling cascade.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study11

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

  1. 01AnimalAnimal study (in vivo)Mechanism

    In wild-type mice, continuous exendin‑4 increased beta-cell mass.

    In plain wordsIn mice, continuous exendin‑4 increased the mass of insulin-producing cells.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseBeta-cell mass
    Study

    mousen: not reported in source

    Wild-type mice
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated · 28 daysAs given in this study (mouse).

    Measurements

    Beta-cell mass increase
    2 fold
    wild-type mice

    Source sentences

    Summary
    In wild type mice Ex4 administered continuously for 28 days increased beta cell mass 2-fold.
  2. 02AnimalAnimal study (in vivo)Mechanism

    In Irs2-deficient mice, exendin‑4 failed to stop progressive beta-cell loss.

    In plain wordsIn mice lacking Irs2, exendin‑4 did not stop progressive loss of insulin-producing cells.

    Peptide
    Exenatide (exendin-4)
    Outcome
    No significant changeProgressive beta-cell loss
    Study

    mousen: not reported in source

    Irs2(-/-) mice
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By contrast, Ex4 failed to arrest the progressive beta cell loss in Irs2(-/-) mice, which culminated in fatal diabetes; however, Ex4 delayed the progression of diabetes by 3 weeks by promoting insulin secretion from the remaining islets.
  3. 03AnimalAnimal study (in vivo)Safety outcome

    In Irs2-deficient mice, beta-cell loss progressed to fatal diabetes despite exendin‑4.

    In plain wordsIn mice lacking Irs2, diabetes became fatal despite exendin‑4 treatment.

    Peptide
    Exenatide (exendin-4)
    Outcome
    Not applicableFatal diabetes
    Study

    mousen: not reported in source

    Irs2(-/-) mice
    Outcome group
    Mortality · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By contrast, Ex4 failed to arrest the progressive beta cell loss in Irs2(-/-) mice, which culminated in fatal diabetes; however, Ex4 delayed the progression of diabetes by 3 weeks by promoting insulin secretion from the remaining islets.
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In Irs2-deficient mice, exendin‑4 delayed diabetes progression.

    In plain wordsIn mice lacking Irs2, exendin‑4 delayed diabetes progression.

    Peptide
    Exenatide (exendin-4)
    Outcome
    DecreaseDiabetes progression
    Study

    mousen: not reported in source

    Irs2(-/-) mice
    Outcome group
    Glycemic control · Metabolic and weight
    Studied dose
    Dose not stated

    Measurements

    Progression delay
    3 weeks
    Irs2(-/-) mice

    Source sentences

    Summary
    By contrast, Ex4 failed to arrest the progressive beta cell loss in Irs2(-/-) mice, which culminated in fatal diabetes; however, Ex4 delayed the progression of diabetes by 3 weeks by promoting insulin secretion from the remaining islets.
  5. 05AnimalAnimal study (in vivo)Mechanism

    In Irs2-deficient mice, exendin‑4 promoted insulin secretion from remaining islets.

    In plain wordsIn mice lacking Irs2, exendin‑4 promoted insulin release from remaining islets.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseInsulin secretion
    Study

    mousen: not reported in source

    Irs2(-/-) mice
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By contrast, Ex4 failed to arrest the progressive beta cell loss in Irs2(-/-) mice, which culminated in fatal diabetes; however, Ex4 delayed the progression of diabetes by 3 weeks by promoting insulin secretion from the remaining islets.
  6. 06LabEx vivo tissueMechanism

    In isolated human islets, exendin‑4 increased cAMP levels.

    In plain wordsIn lab tests, exendin‑4 increased cAMP in human islets.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreasecAMP human islets
    Study

    humann: not reported in source

    Human islets
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation.
  7. 07LabEx vivo tissueMechanism

    In human islets, exendin‑4-associated cAMP increases promoted Irs2 expression.

    In plain wordsIn lab tests, exendin‑4 increased a signal that promoted Irs2 expression in human islets.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseIrs2 expression human islets
    Study

    humann: not reported in source

    Human islets
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation.
  8. 08LabEx vivo tissueMechanism

    In human islets, exendin‑4-associated cAMP increases stimulated Akt phosphorylation.

    In plain wordsIn lab tests, exendin‑4 increased a signal that stimulated Akt phosphorylation in human islets.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseAkt phosphorylation human islets
    Study

    humann: not reported in source

    Human islets
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation.
  9. 09LabIn vitro (cells)Mechanism

    In Min6 cells, exendin‑4 increased cAMP levels.

    In plain wordsIn cells, exendin‑4 increased cAMP levels.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreasecAMP Min6 cells
    Study

    n: not reported in source

    Min6 cells
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation.
  10. 10LabIn vitro (cells)Mechanism

    In Min6 cells, exendin‑4-associated cAMP increases promoted Irs2 expression.

    In plain wordsIn cells, exendin‑4 increased a signal that promoted Irs2 expression.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseIrs2 expression Min6 cells
    Study

    n: not reported in source

    Min6 cells
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation.
  11. 11LabIn vitro (cells)Mechanism

    In Min6 cells, exendin‑4-associated cAMP increases stimulated Akt phosphorylation.

    In plain wordsIn cells, exendin‑4 increased a signal that stimulated Akt phosphorylation.

    Peptide
    Exenatide (exendin-4)
    Outcome
    IncreaseAkt phosphorylation Min6 cells
    Study

    n: not reported in source

    Min6 cells
    Outcome group
    Receptor activity and mechanism · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Ex4 increased cAMP levels in human islets and Min6 cells, which promoted Irs2 expression and stimulated Akt phosphorylation.

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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