Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.
Bottom Line: Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days.Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week.Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin.
Affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.Show MeSH
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Mentions: Finally, we assessed muscle metabolic insulin sensitivity by calculating glucose infusion rate during the insulin clamps and Western blot analysis of Akt and ERK1/2 phosphorylation in muscle in all study animals. As shown in Figure 6, compared with chow-fed controls, insulin-stimulated glucose disposal did not change significantly before day 3 but then declined significantly and progressively afterwards (by ∼20% at week 1, ∼40% at week 2 and ∼60% at week 4, P<0.05 for all) in HFD-fed rats. Animals that received the HFD and sodium salicylate exhibited a marked improvement in insulin-stimulated glucose disposal by week 2 (∼50% increase) and week 4 (∼70% increase; P<0.05 for both). Interestingly, neither HFD nor HFD plus sodium salicylate affected insulin-mediated Akt or ERK1/2 phosphorylation in muscle (Figure 7).
Affiliation: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22903, U.S.A.