Access to the PDF text

Free Article !

Archives of cardiovascular diseases
Volume 102, n° S1
page 22 (mars 2009)
Doi : 10.1016/S1875-2136(09)72176-X
Themes et posters

B005 Dietary-induced insulin resistance associated with dyslipidemia induces progressive cardiac dysfunction in rats as evidenced by echocardiography

S. Grauzam 1, M.-C. Toufektsian 1, O. Ormezzano 2, M.-G. Jouan 1, F. Boucher 1, T. Sulpice 3
1 Laboratoire TIMC-PRETA, La Tronche, France 
2 Centre Hospitalier Universitaire, Grenoble, France 
3 Physiogenex SAS, Toulouse, France 


A major complication of diabetes is the development of cardiac dysfunction in absence of vascular disease. Metabolic disorders such as insulin resistance (IR) and dyslipidemia (DL) might contribute to the induction of diabetic cardiomyopathy (DCM). However, few relevant animal models are currently available for studying the time-course of DCM and evaluating experimental therapeutics. We developed a rodent model of dietary-induced IR combined or not with DL in order to investigate the impact of chronic IR and DL on in vivo myocardial function.

Methods & Results

Male Sprague-Dawley rats were fed a western-type diet (65 % fat ; 15 % fructose ; WD: n=12). DL was induced by combining the western diet with i.p. injections of a nonionic surface-active agent (P-407 ; 0.2mg/kg, 3 times/wk ; WD-P407 n=9). A chow diet was used as control (Chow: n=9). At 6, 11 and 14 wks, cardiac function was assessed by echocardiography. After 6 wks, plasma insulin was significantly increased in both WD and WD-P407 groups (P<0.05 vs. Chow). Fasting blood glucose increased in WD group while plasma lipids markedly accumulated in WD-P407-treated rats (P<0.05 and P<0.01 vs. Chow, respectively). Pulse-wave Doppler indicated impaired diastolic function at 14 wks (E/A wave ratio: WD-P407: 1.42±0.06 vs. Chow: 1.65±0.11). M-mode imaging showed no significant differences in cardiac function and geometry under basal conditions. However, fractional shortening (FS) was significantly depressed under dobutamine stress in WD group at 14 wks (FS in % of baseline: 151±9 % vs 196±7 % ; P<0.05) whereas systolic dysfunction appeared as early as 11 wks and worsened at 14 wks in WD-P407 animals (P<0.05 and P<0.01 vs. Chow, respectively). Finally, compared to Chow, myocardial lipid tissue content were significantly higher in WD and WD-P407 groups, the cardiac lipid accumulation being more pronounced in the later.


DL exacerbated cardiac lipotoxicity and functional complications associated with IR. This experimental model of combined IR and DL closely mimics the main clinical manifestations of DCM and might therefore constitute a useful tool for the evaluation of pharmacological treatments.

The full text of this article is available in PDF format.
The full text of this article is available in PDF format.
Click here to see it.

Top of the page

© 2009  Elsevier Masson SAS. All Rights Reserved.
EM-CONSULTE.COM is registrered at the CNIL, déclaration n° 1286925.
As per the Law relating to information storage and personal integrity, you have the right to oppose (art 26 of that law), access (art 34 of that law) and rectify (art 36 of that law) your personal data. You may thus request that your data, should it be inaccurate, incomplete, unclear, outdated, not be used or stored, be corrected, clarified, updated or deleted.
Personal information regarding our website's visitors, including their identity, is confidential.
The owners of this website hereby guarantee to respect the legal confidentiality conditions, applicable in France, and not to disclose this data to third parties.
Article Outline
You can move this window by clicking on the headline