What question did this study set out to answer?

To determine whether GLP-1 receptor agonism with exendin-4 reverses diabetic cardiomyopathy independently of diabetes etiology in genetic and diet-induced models.

May 25, 2013AJP Heart and Circulatory PhysiologyOpen Access

Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes

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Why the study?

Does exendin-4 improve cardiac remodeling and dysfunction in mouse models of type 2 diabetes?

Population

Two types of diabetic cardiomyopathy mouse models: genetic and acquired T2DM induced by high-fat diet

Comparison

Exendin-4 (24 nmol·kg(-1)·day(-1) for 40 days) vs Vehicle

Design

Preclinical

Follow-up

40 days

Authors

AMAkio MonjiBrigham and Women's Hospital TMToko MitsuiMeijo Hospital YBYoshiyuki BandoMie University

Discussion

Member takes

Implication

Warrants human trials of GLP-1 agonism in diabetic cardiomyopathy; leaves open translation beyond mouse models.

Key Points

To determine whether GLP-1 receptor agonism with exendin-4 reverses diabetic cardiomyopathy independently of diabetes etiology in genetic and diet-induced models.
Studied genetic (KK) and diet-induced obesity (DIO) mouse models of type 2 diabetes mellitus.
Treated mice with either exendin-4 (24 nmol·kg⁻¹·day⁻¹) or vehicle control for 40 days.
Exendin-4 restored systolic dysfunction in DIO mice and diastolic left ventricular dysfunction in both DIO and KK models while reducing left ventricular hypertrophy.
Treatment reversed myocardial fibrosis, cardiac steatosis, and mitochondrial remodeling across both diabetic models.
Exendin-4 reduced myocardial oxidative stress via NADPH oxidase 4 suppression, elevated SOD-1 and glutathione peroxidase, and suppressed inflammatory cytokines ICAM-1 and M-CSF.

Structured PICO

Does exendin-4 improve cardiac remodeling and dysfunction in mouse models of type 2 diabetes?

Population

Two types of diabetic cardiomyopathy mouse models: genetic (KK) and acquired T2DM induced by high-fat diet (diet-induced obesity [DIO])

Intervention

Exendin-4 (24 nmol·kg(-1)·day(-1) for 40 days)

Comparator

Vehicle

Outcome

Cardiac remodeling and dysfunction (systolic and diastolic left ventricular function, left ventricular hypertrophy, myocardial fibrosis, steatosis, and oxidative stress)surrogate

GLP-1R activation with exendin-4 reverses cardiac remodeling and dysfunction in type 2 diabetes mouse models by normalizing lipid metabolism and reducing oxidative stress.

Cite This Study

Monji et al. (2013) studied this question.

synapsesocial.com/papers/6a8d377150db337a287dca72 https://doi.org/10.1152/ajpheart.00990.2012

Topics

Lipid management GLP-1 agonists cardiovascular outcomes

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Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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Topics

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