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Decreased CD 36 and Insulin Receptor Expression in Insulin Resistant OLETF Rats
Author(s) -
Popovich Irina,
Rodriguez Ruben,
Viscarra Jose,
Ortiz Rudy
Publication year - 2011
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.25.1_supplement.825.17
Free fatty acids (FFA) provide the primary source of energy; however, insulin resistance (IR) may alter substrate utilization, compromising cardiovascular function. Furthermore, angiotensin receptor blockers (ARB) improve insulin signaling in peripheral tissues, but its affects in the heart with respect to insulin signaling and FFA metabolism are not well described. Because lipid metabolism is altered during insulin resistance and CD36 (Fatty Acid Translocase) is important for FFA transport, we tested the hypothesis that insulin resistance decreases CD36 expression in the heart in a model of metabolic syndrome (OLETFs). Over 6 wk, we studied 6 groups of rats: 1) LETO (lean strain controls), 2) OLETF baseline (OLETF BL; 9 wks of age), 3) OLETF (15 wks of age), 4) OLETF + ARB (10 mg olmesartan/kg/d), 5 OLETF + high glucose (HG; 5% in water), and 6) OLETF + ARB + HG. Compared to OLETF, ARB treatment decreased CD36 20% and 36% when supplemented with HG suggesting that activation of Ang II receptor facilitates FFA uptake in cardiomyocytes. HG increased CD36 15% compared to OLETF. Paradoxically, ARB decreased insulin receptor 36% in both supplemented and unsupplemented groups suggesting that blockade of Ang II receptor impairs insulin signaling in the heart. Results suggest that the Ang II receptor contributes to substrate utilization in the heart during insulin resistance. Funded by NIH NCMHD 9T37MD001480 & P20MD005049.