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Insulin resistance as a mechanism of preserved myocardial function in heart failure animals fed a high fat diet
Author(s) -
Christopher Bridgette A,
Huang HsuanMing,
McElfresh Tracy A,
Chen Xiaoqin,
Muzic Raymond F,
Croniger Colleen M,
Chandler Margaret P
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.601.3
Subject(s) - insulin resistance , glut4 , medicine , heart failure , endocrinology , contractility , insulin , insulin receptor , protein kinase b , cardiac function curve , chemistry , signal transduction , biochemistry
Heart failure (HF) rats fed a high saturated fat diet (SAT) have improved left ventricular contractile function compared to HF animals fed normal chow (NC) diets. Both HF and SAT are individually associated with the development of insulin resistance (IR), but the role of IR in HF+SAT is unknown. We hypothesize that the cardioprotective effect seen in HF+SAT results from defects in insulin signaling that decrease glucose uptake in IR myocardium. Rats underwent coronary ligation or sham (SH) surgery & were fed NC or SAT for 8 weeks. Cardiac contractility (peak positive dP/dt) was preserved in HF+SAT animals versus HF+NC. SH+SAT, HF+NC & HF+SAT animals have abnormal glucose tolerance tests & elevated insulin levels compared to SH+NC, indicating peripheral IR. MicroPET data shows HF+SAT animals have myocardial IR relative to all other groups. Protein targets of insulin signaling (IRS‐1, Akt, pAkt, GLUT4) are currently being analyzed. HF+SAT animals are IR in both peripheral tissue & the myocardium, while SH+SAT & HF+NC animals are IR in the periphery only. This correlates to preserved contractile function in HF+SAT versus HF+NC. We predict that insulin signaling targets such as pAkt and GLUT4 are downregulated, which may be the mechanism by which myocardial insulin resistance preserves contractile function in HF+SAT animals. (Grant # NHLBI HL‐081857)