| Autor: |
Gopan, Thottathil, Ioachimescu, Adriana G., Gornik, Heather, Makdissi, Antoine, Davidson, Michael B., Pinero, Mercedes, Fleseriu, Maria, Febbraio, Maria, Silverstein, Roy, Kashyap, Sangeeta R. |
| Předmět: |
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| Zdroj: |
Diabetes; Jun2007 Supplement 1, Vol. 56, pA190-A191, 2p |
| Abstrakt: |
To explore the vascular effects of sustained elevations of plasma free fatty acids (FFA) on atherogenesis relative to induction of insulin resistance (IR), we infused Intralipid- heparin (LIP) and saline (SAL) for 24 hrs in five healthy subjects (Age 44.44±7.4 yrs; 2M,3F; BMI, 22.6±3.1 kg/m²; fasting plasma glucose, 95.4±7.7 mg/dL; fasting insulin, 5.3±1.3 µU/mL). After each infusion, endothelium-dependent flow-mediated vasodilatation (FMD) of the brachial artery was measured using high resolution ultrasound followed by an 80 mU/m²/min euglycemic hyperinsulinemic clamp to assess whole body insulin sensitivity. Peripheral blood monocytes were isolated prior to insulin infusion during LIP and SAL for determination of scavenger receptor A and B (CD36) expression on CD14 positive cells by FACS analysis using flouroscein conjugated antibodies and appropriate isotype controls. Infusion of LIP raised plasma FFA levels (1.30±.26 mEq/L) compared to SAL (0.20± 16 mEq/L) simulating levels seen in obesity and type 2 diabetes. Whole body insulin-stimulated glucose disposal (M) was reduced by 15% during LIP vs. SAL (7.14±1.2 vs. 8.7±2.8 mg.kg[sup -l].min[sup -1] per µU/ml). FMD of the brachial artery was significantly impaired by LIP vs. SAL infusion (8.1±0.5% vs. 9.4±1.7%). Mean channel fluorescence for cell surface scavenger receptor CD36 expression on CD14 positive cells was markedly increased with LIP vs. SAL infusion (467±98 vs. 272±69) with no change in SRA expression. There was no correlation between decrease in M value during LIP infusion and either decrease in FMD or increase in CD36 expression. This suggests that plasma FFA mediate endothelial dysfunction and inflammation independently of their effect on induction of IR, suggesting a different mechanism of action and signaling of FFA on vascular vs. metabolically active tissues. Elucidation of these mechanisms may contribute to better understanding of pathogenesis and treatment of accelerated atherosclerosis in diabetics. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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