Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats

Abstract

Nadeau. Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 290: H2571-H2581, 2006. First published January 27, 2006 doi:10.1152/ajpheart.01002.2005.-This study was designed to investigate the effects of a sucrose diet on vascular and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age-matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a first series of experiments, the three groups of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine glucose transport activity in isolated muscles and to determine endothelial nitric oxide synthase (eNOS) protein expression in muscles and endothelin content in vascular tissues. Sucrose feeding was shown to markedly enhance the pressor response to insulin and its hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction in eNOS protein content in muscle, but no change in vascular endothelin-1 protein, was noted in sucrose-fed SHR when compared with WKY rats, but these changes were not different from those noted in chow-fed SHR. Similar reductions in insulin-stimulated glucose transport were observed in soleus muscles from both groups of SHR when compared with WKY rats. In extensor digitorum longus muscles, a significant reduction in insulin-stimulated glucose transport was only seen in sucrose-fed rats when compared with the other two groups. Environmental factors, that is, high intake of simple sugars, could possibly potentiate the genetic predisposition in SHR to endothelial dysfunction and insulin resistance.hypertension; insulin vascular effects; nitric oxide synthase INSULIN IS CHARACTERISTICALLY recognized for its ability to stimulate glucose uptake into insulin-sensitive tissues. On a quantitative basis, skeletal muscle has been identified as the main site of insulin-stimulated glucose disposal and as a major tissue responsible for postprandial hyperglycemia in insulinresistant states (11). In addition to its effects on glucose metabolism, insulin was shown to vasodilate skeletal muscle vasculature in insulin-sensitive, but not in insulin-resistant, subjects (3). The vasodilating action of insulin has been confirmed by us in conscious rats (35) and by others in humans over a range of physiological insulin concentrations and by using different techniques (1, 51, 52). There is evidence that, among the most likely mechanisms responsible for the hemodynamic responses, there is a role for endothelium-derived nitric oxide (NO) in the mediation of insulin-induced skeletal muscle vasodilation (44, 46). Furthermore, insulin was shown to modulate the expression of the enzy...

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“…Homogenates were centrifuged (10,000 g for 10 min, 4°C), and protein concentrations of the supernatant were determined by the bicinchoninic acid method (Pierce), using BSA as the standard. Protein samples (45 g) were separated by SDS-PAGE and electrophoretically transferred (100 V, 2 h) to polyvinylidene difluoride (PVDF) membranes (35,47). PVDF membranes were incubated at 4°C overnight with monoclonal antibodies against eNOS (1:500; Transduction Labs, Lexington, KY), nitrotyrosine (1:500; Calbiochem, San Diego, CA) (35), or polyclonal anti-gp91 phox (1:500; Transduction Labs).…”

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