Exendin-4, a GLP-1 receptor agonist regulates retinal capillary tone and restores microvascular patency after ischaemia-reperfusion injury.

Zhai R, Xu H, Hu F, Wu J, Kong X, Sun X

British journal of pharmacology27 May 2020Cited by 35 (Europe PMC)

PMID32232832PMCIDPMC7348095DOI10.1111/bph.15059PepBankPUB-32232832

Summary

Background and purposeThe aim of this study is to investigate the vasorelaxant effect of exendin-4, a GLP-1 receptor agonist on retinal capillaries under normal and ischaemia-reperfusion (I/R) conditions.Experimental approachCapillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy. A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber. To assess the effects of exendin-4, it was administered through subcutaneous injection, intravitreal injection, or eye drops. The underlying mechanism was explored by immunofluorescence, qPCR, and capillary western blots.Key resultsImmunofluorescence staining showed that GLP-1 receptors were expressed in endothelial cells of retinal capillaries. Exendin-4 relaxed the capillaries precontracted by noradrenaline, an effect abolished by denuding endothelium with CHAPS and inhibited by GLP-1 receptor antagonist exendin-9-39, endothelial NOS (eNOS) inhibitor l-NAME, and the guanylate cyclase blocker ODQ but not by a COX inhibitor, indomethacin. Retinal capillaries were constricted in I/R injury, an effect reversed by perfusion of exendin-4. Expression of PI3K and Akt, phosphorylation level of eNOS and NO production after I/R were lower than that in the normal control group. Administration of exendin-4 improved the changes.Conclusion and implicationsExendin-4 can restore injured microvascular patency in I/R. Exendin-4 may regulate retinal capillaries through the GLP-1 receptor-PI3K/Akt-eNOS/NO-cGMP pathway. Therefore, exendin-4 may be an effective treatment for improving tissue perfusion in I/R-related conditions.

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.

01AnimalAnimal study (in vivo)Mechanism
In the rat retinal I/R model, exendin‑4 improved the injury-associated reduction in PI3K expression.
In plain wordsIn rats with retinal injury, exendin‑4 improved reduced PI3K expression.
Peptide
Exenatide (exendin-4)
Outcome
IncreasePI3K expression after I/R
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Studied dose
Dose not stated
Source sentences
Summary
Administration of exendin-4 improved the changes.
3 context sentences(design, population, supporting numbers)
Summary · context
Expression of PI3K and Akt, phosphorylation level of eNOS and NO production after I/R were lower than that in the normal control group.
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
Show in the study text Report a problemFND-3223283208
02AnimalAnimal study (in vivo)Mechanism
In the rat retinal I/R model, exendin‑4 improved the injury-associated reduction in Akt expression.
In plain wordsIn rats with retinal injury, exendin‑4 improved reduced Akt expression.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseAkt expression after I/R
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Studied dose
Dose not stated
Source sentences
Summary
Administration of exendin-4 improved the changes.
3 context sentences(design, population, supporting numbers)
Summary · context
Expression of PI3K and Akt, phosphorylation level of eNOS and NO production after I/R were lower than that in the normal control group.
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
Show in the study text Report a problemFND-3223283209
03AnimalAnimal study (in vivo)Mechanism
In the rat retinal I/R model, exendin‑4 improved the injury-associated reduction in eNOS phosphorylation.
In plain wordsIn rats with retinal injury, exendin‑4 improved reduced eNOS phosphorylation.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseeNOS phosphorylation after I/R
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Studied dose
Dose not stated
Source sentences
Summary
Administration of exendin-4 improved the changes.
3 context sentences(design, population, supporting numbers)
Summary · context
Expression of PI3K and Akt, phosphorylation level of eNOS and NO production after I/R were lower than that in the normal control group.
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
Show in the study text Report a problemFND-3223283210
04AnimalAnimal study (in vivo)Mechanism
In the rat retinal I/R model, exendin‑4 improved the injury-associated reduction in NO production.
In plain wordsIn rats with retinal injury, exendin‑4 improved reduced nitric oxide production.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseNO production after I/R
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Studied dose
Dose not stated
Source sentences
Summary
Administration of exendin-4 improved the changes.
3 context sentences(design, population, supporting numbers)
Summary · context
Expression of PI3K and Akt, phosphorylation level of eNOS and NO production after I/R were lower than that in the normal control group.
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
Show in the study text Report a problemFND-3223283211
05LabEx vivo tissueActivity measurement
In isolated retinal capillaries, exendin‑4 relaxed capillaries precontracted by noradrenaline.
In plain wordsIn lab tests, exendin‑4 relaxed retinal capillaries that noradrenaline had contracted.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseNoradrenaline-precontracted capillary relaxation
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Vascular function · Eye
Studied dose
Dose not stated
Source sentences
Summary
Exendin-4 relaxed the capillaries precontracted by noradrenaline,
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
Show in the study text Report a problemFND-3223283201
06LabEx vivo tissueEfficacy outcome
In retinal capillaries after ischaemia-reperfusion injury, exendin‑4 perfusion reversed constriction.
In plain wordsIn lab tests, exendin‑4 reversed retinal capillary narrowing after ischaemia-reperfusion injury.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseI/R-induced capillary constriction
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Vascular function · Eye
Studied dose
Dose not stated
Source sentences
Summary
Retinal capillaries were constricted in I/R injury, an effect reversed by perfusion of exendin-4.
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
Show in the study text Report a problemFND-3223283207

Studies that did not test the peptide alone5

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).

07LabNot a test of Exenatide (exendin-4) aloneEx vivo tissueMechanism
In retinal capillaries, removing endothelium abolished exendin‑4-induced relaxation.
In plain wordsIn lab tests, removing the vessel lining abolished the relaxation caused by exendin‑4.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableEndothelium dependence
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Source sentences
Summary
Exendin-4 relaxed the capillaries precontracted by noradrenaline, an effect abolished by denuding endothelium with CHAPS and inhibited by GLP-1 receptor antagonist exendin-9-39, endothelial NOS (eNOS) inhibitor l-NAME, and the guanylate cyclase blocker ODQ but not by a COX inhibitor, indomethacin.
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
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).
Show in the study text Report a problemFND-3223283202
08LabNot a test of Exenatide (exendin-4) aloneEx vivo tissueMechanism
In retinal capillaries, exendin-9-39 inhibited exendin‑4-induced relaxation.
In plain wordsIn lab tests, a GLP-1 receptor blocker inhibited the relaxation caused by exendin‑4.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableGLP-1 receptor dependence
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Source sentences
Summary
Exendin-4 relaxed the capillaries precontracted by noradrenaline, an effect abolished by denuding endothelium with CHAPS and inhibited by GLP-1 receptor antagonist exendin-9-39, endothelial NOS (eNOS) inhibitor l-NAME, and the guanylate cyclase blocker ODQ but not by a COX inhibitor, indomethacin.
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
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).
Show in the study text Report a problemFND-3223283203
09LabNot a test of Exenatide (exendin-4) aloneEx vivo tissueMechanism
In retinal capillaries, l-NAME inhibited exendin‑4-induced relaxation.
In plain wordsIn lab tests, an eNOS inhibitor inhibited the relaxation caused by exendin‑4.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableeNOS dependence
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Source sentences
Summary
Exendin-4 relaxed the capillaries precontracted by noradrenaline, an effect abolished by denuding endothelium with CHAPS and inhibited by GLP-1 receptor antagonist exendin-9-39, endothelial NOS (eNOS) inhibitor l-NAME, and the guanylate cyclase blocker ODQ but not by a COX inhibitor, indomethacin.
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
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).
Show in the study text Report a problemFND-3223283204
10LabNot a test of Exenatide (exendin-4) aloneEx vivo tissueMechanism
In retinal capillaries, ODQ inhibited exendin‑4-induced relaxation.
In plain wordsIn lab tests, a guanylate cyclase blocker inhibited the relaxation caused by exendin‑4.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableGuanylate cyclase dependence
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Source sentences
Summary
Exendin-4 relaxed the capillaries precontracted by noradrenaline, an effect abolished by denuding endothelium with CHAPS and inhibited by GLP-1 receptor antagonist exendin-9-39, endothelial NOS (eNOS) inhibitor l-NAME, and the guanylate cyclase blocker ODQ but not by a COX inhibitor, indomethacin.
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
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).
Show in the study text Report a problemFND-3223283205
11LabNot a test of Exenatide (exendin-4) aloneEx vivo tissueMechanism
In retinal capillaries, indomethacin did not inhibit exendin‑4-induced relaxation.
In plain wordsIn lab tests, a COX inhibitor did not inhibit the relaxation caused by exendin‑4.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeCOX inhibition response
Study
ratn: not reported in source
Retinal capillaries
Outcome group
Receptor activity and mechanism · Eye
Source sentences
Summary
Exendin-4 relaxed the capillaries precontracted by noradrenaline, an effect abolished by denuding endothelium with CHAPS and inhibited by GLP-1 receptor antagonist exendin-9-39, endothelial NOS (eNOS) inhibitor l-NAME, and the guanylate cyclase blocker ODQ but not by a COX inhibitor, indomethacin.
2 context sentences(design, population, supporting numbers)
Summary · context
Capillary diameters in the whole-mounted retina were directly observed using infrared differential interference contrast microscopy.
Summary · context
A model of retinal I/R was established inraats,using high perfusion pressure in an anterior chamber.
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).
Show in the study text Report a problemFND-3223283206

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.

Version 2Current
22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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