Exenatide improves glucose homeostasis and prolongs survival in a murine model of dilated cardiomyopathy.

Vyas AK, Yang KC, Woo D, Tzekov A, Kovacs A, Jay PY, Hruz PW

PloS one17 Feb 2011Cited by 54 (Europe PMC)

PMID21359201PMCIDPMC3040766DOI10.1371/journal.pone.0017178PepBankPUB-21359201

Summary

BackgroundThere is growing awareness of secondary insulin resistance and alterations in myocardial glucose utilization in congestive heart failure. Whether therapies that directly target these changes would be beneficial is unclear. We previously demonstrated that acute blockade of the insulin responsive facilitative glucose transporter GLUT4 precipitates acute decompensated heart failure in mice with advanced dilated cardiomyopathy. Our current objective was to determine whether pharmacologic enhancement of insulin sensitivity and myocardial glucose uptake preserves cardiac function and survival in the setting of primary heart failure.Methodology/principal findingsThe GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life. TG9 mice develop congestive heart failure and secondary insulin resistance in a highly predictable manner with death by 12 weeks of age. Glucose homeostasis was assessed by measuring glucose tolerance at 8 and 10 weeks and tissue 2-deoxyglucose uptake at 75 days. Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice. Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals. Total myocardial GLUT1 levels were not different between groups. Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice.Conclusion/significanceIn heart failure secondary insulin resistance is maladaptive and myocardial glucose uptake is suboptimal. An incretin-based therapy, which addresses these changes, appears beneficial.

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.

01AnimalAnimal study (in vivo)Efficacy outcome
In TG9 mice, exenatide improved glucose tolerance compared with vehicle.
In plain wordsIn mice with cardiomyopathy, exenatide improved glucose tolerance compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseGlucose tolerance
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated
Source sentences
Summary
Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920101
02AnimalAnimal study (in vivo)Mechanism
In TG9 mice, exenatide improved myocardial GLUT4 expression compared with vehicle.
In plain wordsIn mice with cardiomyopathy, exenatide improved heart GLUT4 expression compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseMyocardial GLUT4 expression
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920102
03AnimalAnimal study (in vivo)Efficacy outcome
In TG9 mice, exenatide improved myocardial 2-deoxyglucose uptake compared with vehicle.
In plain wordsIn mice with cardiomyopathy, exenatide improved heart uptake of 2-deoxyglucose compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseMyocardial 2-deoxyglucose uptake
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920103
04AnimalAnimal study (in vivo)Efficacy outcome
In TG9 mice, exenatide improved cardiac contractility compared with vehicle.
In plain wordsIn mice with cardiomyopathy, exenatide improved heart contraction compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseCardiac contractility
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920104
05AnimalAnimal study (in vivo)Efficacy outcome
In TG9 mice, exenatide improved survival compared with vehicle.
In plain wordsIn mice with cardiomyopathy, exenatide improved survival compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseSurvival
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920105
06AnimalAnimal study (in vivo)Mechanism
In TG9 mice, exenatide increased AMP kinase phosphorylation.
In plain wordsIn mice with cardiomyopathy, exenatide increased AMP kinase phosphorylation compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseAMP kinase phosphorylation
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920106
07AnimalAnimal study (in vivo)Mechanism
In TG9 mice, exenatide increased AKT phosphorylation.
In plain wordsIn mice with cardiomyopathy, exenatide increased AKT phosphorylation compared with vehicle.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseAKT phosphorylation
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Receptor activity and mechanism · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920107
08AnimalAnimal study (in vivo)Mechanism
In TG9 mice, myocardial GLUT1 levels did not differ between exenatide and control groups.
In plain wordsIn mice with cardiomyopathy, heart GLUT1 levels did not differ between exenatide and control groups.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeMyocardial GLUT1 levels
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Vehicle-treated TG9 mice
Outcome group
Heart function · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Total myocardial GLUT1 levels were not different between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920108
09AnimalAnimal study (in vivo)Efficacy outcome
In TG9 mice, exenatide abrogated ritonavir's detrimental effect on survival.
In plain wordsIn mice with cardiomyopathy, exenatide prevented the harmful survival effect of ritonavir compared with ritonavir alone.
Peptide
Exenatide (exendin-4)
Outcome
IncreaseSurvival during ritonavir challenge
Study
mousen: not reported in source
TG9 dilated cardiomyopathy mice
Comparator
Ritonavir without exenatide
Outcome group
Mortality · Cardiovascular
Studied dose
Dose not stated
Source sentences
Summary
Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
The GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life.
Show in the study text Report a problemFND-2135920109

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

Subjects

Terms as the source lists them.

PepBank is a research reference. Talk to a doctor before you use any peptide.