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Obesity is an important risk factor for insulin resistance and hypertension and plays a central role in the metabolic syndrome. Insight into the pathophysiology of this syndrome may lead to new treatments. This paper has reviewed the evidence for an important role for the microcirculation as a possible link between obesity, insulin resistance and(More)
The intertwined epidemics of obesity and related disorders such as hypertension, insulin resistance, type 2 diabetes, and subsequent cardiovascular disease pose a major public health challenge. To meet this challenge, we must understand the interplay between adipose tissue and the vasculature. Microvascular dysfunction is important not only in the(More)
Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude. Because it could affect O2 transport in several different and potentially conflicting ways, we examined its effects on pulmonary and muscle gas exchange and acid-base status during cycle exercise at approximately 30, 50 and 90% VO2max in normoxia (F(IO2) = 0.2093) and acute hypoxia(More)
Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysi-ologic link between insulin resistance and hypertension in obesity. Many(More)
1 O besity is associated with insulin resistance, hypertension, cardio-vascular disease, and type 2 diabetes (1), but the mechanisms underlying these associations are incompletely understood. This article reviews and adds original data (i.e., in the postprandial state) to the evidence for microvascular dysfunction, including impairment of insulin-stimulated(More)
CONTEXT Angiotensin II (AngII) increases insulin-mediated glucose uptake in healthy individuals. The underlying mechanisms are undefined. AngII may increase glucose uptake through a direct effect on muscle cell insulin signaling or through increasing insulin delivery to muscle cells through effects on the microvasculature. OBJECTIVE Our objective was to(More)
OBJECTIVE An effect of insulin that is crucial for stimulating glucose uptake is its ability to increase the number of perfused capillaries, and thereby enhance its own delivery, and that of glucose, to muscle cells. To unravel possible mechanisms involved in the insulin-sensitizing effects of angiotensin II receptor blockers (ARBs) in hypertensive(More)
Adequate microvascular perfusion is essential for the regulation of tissue metabolism. Therefore, defects in microvascular function may play a role in obesity-associated insulin resistance. Steady-state hyperinsulinemia during a euglycemic hyperinsulinemic clamp stimulates endothelium-dependent vasodilation and capillary recruitment, which contribute to(More)
Facilitated hexose transporter proteins may have clusters of hydrophobic residues lining the exofacial entrance to their pores, which act as substrate selectivity filters. Glucose is a signal that is detected at several anatomical sites and activates neuronal circuits involved in the control of glucose and energy homeostasis. This review looks at the(More)
adapted from Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity-associated insulin resistance and hypertension. Opening remarks This thesis describes the studies performed at the VU medical center during my PhD project. It is the latest in a line of projects testing our group's main hypothesis: the microvasculature as a pivot at(More)