Cardiac contractile function and mitochondrial respiration in diabetes-related mouse models

Cardiovascular Diabetology

Original Investigation

Camille Marciniak¹  Xavier Marechal¹  Steve Lancel¹  Remi Neviere¹  David Montaigne¹ 

[1] EA 4484 – Physiology Department, Faculty of Medicine, Lille 2 University, 1, place de Verdun, 59045, Lille, France;

关键词: Metabolic syndrome;    Diabetes;    Heart;    Mitochondria;    Respiration;    Streptozotocin;    High-fat diet;   

DOI  :  10.1186/s12933-014-0118-7

 received in 2014-03-26, accepted in 2014-07-23,  发布年份 2014

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Marciniak et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.