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Cardiovascular Diabetology

, 13:118

First Online: 21 August 2014Received: 26 March 2014Accepted: 23 July 2014


BackgroundPathophysiological processes underlying diabetic-related cardiomyopathies are complex. Mitochondria dysfunction is often described as a cause of cardiac impairment but its extent may depend on the type of experimental diabetes. Here we proposed to compare drug- or diet-induced models of diabetes in terms of metabolic features, cardiac and mitochondrial functions.

MethodsMice were fed with regular chow or fat-enriched diet. After three weeks, they received either citrate or streptozotocin injections for five consecutive days. Metabolic parameters, myocardial contractile function and mitochondrial respiration were measured after three more weeks. Fat mass volumes were assessed by magnetic resonance imaging. Oral glucose tolerance test, insulin tolerance test, triglyceride and adipocytokine quantification were evaluated to establish metabolic profiles. Cardiac function was assessed ex vivo onto a Langendorff column. Isolated cardiac mitochondria respiration was obtained using high-resolution oxygraphy.

ResultsMice fed with the fat-enriched regimen presented abdominal obesity, increased blood glucose, elevated leptin level, glucose intolerance, and insulin resistance. Mice treated with streptozotocin, independently of the regimen, lost their capacity to release insulin in response to glucose ingestion. Mice fed with regular chow diet and injected with streptozotocin developed cardiac dysfunction without mitochondrial respiration defect. However, both groups of high-fat diet fed mice developed cardiac alterations associated with reduction in mitochondrial oxygen consumption, despite an increase in mitochondrial biogenesis signalling.

ConclusionsWe explored three animal models mimicking type 1 and 2 diabetes. While cardiac dysfunction was present in the three groups of mice, mitochondrial respiration impairment was only obvious in models reproducing features of type 2 diabetes.

KeywordsMetabolic syndrome Diabetes Heart Mitochondria Respiration Streptozotocin High-fat diet AbbreviationsADPAdenosine diphosphate

ANOVAAnalysis of variance

DNADeoxyribonucleic acid

EDTAEthylenediaminetetraacetic acid

EIAEnzyme immunoassay

HFDHigh-fat diet


ITTInsulin tolerance test

MCP1Monocyte chemotactic protein-1

MRIMagnetic resonance imaging

NDNormal diet

NIHNational Institutes of Health

OGTTOral glucose tolerance test

PBSPhosphate-buffered saline

PCRPolymerase chain reaction

PGC-1αPeroxisome proliferator-activated receptor gamma coactivator 1

SEMStandard error of the mean


TNF-αTumor necrosis factor-α

Electronic supplementary materialThe online version of this article doi:10.1186-s12933-014-0118-7 contains supplementary material, which is available to authorized users.

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Autor: Camille Marciniak - Xavier Marechal - David Montaigne - Remi Neviere - Steve Lancel


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