Acute Hyperglycemia and Hyperinsulinemia Enhance Vasodilatation in Type 1 Diabetes Mellitus without Increasing Capillary Permeability and Inducing Endothelial Dysfunction

Oomen, P. H. N.; Kant, Gert; Dullaart, Robin; Reitsma, Wd; Smit, Andries J.

doi:10.1006/mvre.2001.2347

Cited by 24 publications

(16 citation statements)

References 42 publications

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“…In normal humans, some earlier studies [27,28] have reported that acute hyperglycemia reduced endothelium-dependent relaxation response. However, uncomplicated type 1 diabetes mellitus is characterized by generalized vasodilatation, and acute hyperglycemia and/or hyperinsulinemia were found to enhance vasodilatation in these patients [29]. In healthy humans, acute hyperglycemia did not affect endothelium-dependent vasodilator response to acetylcholine [30].…”

Section: Discussionmentioning

confidence: 97%

Effects of hyperglycemia on the modulation of vascular function by perivascular adipose tissue

Lee

Lü²,

Su³

et al. 2009

Journal of Hypertension

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Section: Discussionmentioning

confidence: 97%

Effects of hyperglycemia on the modulation of vascular function by perivascular adipose tissue

Lee

Lü²,

Su³

et al. 2009

Journal of Hypertension

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“…Studies with mannitol, however, suggested that the vascular actions of glucose may, in part, be mediated by increased osmolar load. Oomen et al (2002) investigated the effects of acute hyperglycaemia and hyperinsulinaemia, both separately and in combination, on skin microvascular flow, capillary permeability, capillary recruitment, and ED in subjects with type 1 diabetes mellitus. Hyperglycaemia and hyperinsulinaemia alone or in combination increased flow measured with laser Doppler, but without capillary recruitment or evident Binding of insulin to its receptor-insulin receptor substrate (IRS) complex activates the lipid phosphatidylinositol-3-kinase (PI3K) and generates phosphatidylinositol-3,4,5-trisphosphate (PIP 3 ).…”

Section: Acute Hyperglycaemia Can Also Enhance Blood Flowmentioning

confidence: 99%

Twenty-five years since the discovery of endothelium-derived relaxing factor (EDRF): does a dysfunctional endothelium contribute to the development of type 2 diabetes?

Triggle

Howarth²,

Cheng³

et al. 2005

Can. J. Physiol. Pharmacol.

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Twenty-five years ago, the discovery of endothelium-derived relaxing factor opened a door that revealed a new and exciting role for the endothelium in the regulation of blood flow and led to the discovery that nitric oxide (NO) multi-tasked as a novel cell-signalling molecule. During the next 25 years, our understanding of both the importance of the endothelium as well as NO has greatly expanded. No longer simply a barrier between the blood and vascular smooth muscle, the endothelium is now recognized as a complex tissue with heterogeneous properties. The endothelium is the source of not only NO but also numerous vasoactive molecules and signalling pathways, some of which are still not fully characterized such as the putative endothelium-derived relaxing factor. Dysfunction of the endothelium is a key risk factor for the development of macro- and microvascular disease and, by coincidence, the discovery that NO was generated in the endothelium corresponds approximately in time with the increased incidence of type 2 diabetes. Primarily linked to dietary and lifestyle changes, we are now facing a global pandemic of type 2 diabetes. Characterized by insulin resistance and hyperglycaemia, type 2 diabetes is increasingly being diagnosed in adolescents as well as children. Is there a link between dietary-related hyperglycaemic insults to the endothelium, blood flow changes, and the development of insulin resistance? This review explores the evidence for and against this hypothesis.

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“…While the vasodilating effects of insulin are established [9,10], the direct vascular actions of short-term hyperglycaemia are largely unknown. Studies investigating the effects of high glucose on macrovascular and microvascular perfusion have yielded conflicting results: some have shown attenuated vasodilation [11,12,13,14,15,16], some have demonstrated enhanced vasodilation [17,18,19,20], whereas others found no changes in vascular tone [21,22,23]. The present study was designed to gain deeper insights into the immediate effects of high glucose on endothelial NO formation and vascular tone, and its stimulatory role on the vascular effects of insulin.…”

Section: Introductionmentioning

confidence: 96%

Acute effects of glucose and insulin on vascular endothelium

et al. 2004

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Aims/hypothesis. Chronic exposure to high concentrations of glucose has consistently been demonstrated to impair endothelium-dependent, nitric oxide (NO)-mediated vasodilation. In contrast, several clinical investigations have reported that acute exposure to high glucose, alone or in combination with insulin, triggers vasodilation. The aim of this study was to examine whether elevated glucose itself stimulates endothelial NO formation or enhances insulin-mediated endothelial NO release. Methods. We measured NO release and vessel tone ex vivo in porcine coronary conduit arteries (PCAs). Intracellular Ca 2+ was monitored in porcine aortic endothelial cells (PAECs) by fura-2 fluorescence. Expression of the Na + /glucose cotransporter-1 (SGLT-1) was assayed in PAECs and PCA endothelium by RT-PCR. Results. Stimulation of PCAs with D-glucose, but not the osmotic control L-glucose, induced a transient increase in NO release (EC 50 ≈10 mmol/l), mediated by a rise in intracellular Ca 2+ levels due to an influx from the extracellular space. This effect was abolished by inhibitors of the plasmalemmal Na + /Ca 2+ exchanger (dichlorobenzamil) and the SGLT-1 (phlorizin), which was found to be expressed in aortic and coronary endothelium. Alone, D-glucose did not relax PCA, but did augment the effect of insulin on NO release and vasodilation. Conclusions/interpretation. An increased supply of extracellular D-glucose appears to enhance the activity of the endothelial isoform of nitric oxide synthase by increasing intracellular Na + concentrations via SGLT-1, which in turn stimulates an extracellular Ca 2+ influx through the Na + /Ca 2+ exchanger. This mechanism may be responsible for glucose-enhanced, insulin-dependent increases in tissue perfusion (including coronary blood-flow), thus accelerating glucose extraction from the blood circulation to limit the adverse vascular effects of prolonged hyperglycaemia.

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Acute Hyperglycemia and Hyperinsulinemia Enhance Vasodilatation in Type 1 Diabetes Mellitus without Increasing Capillary Permeability and Inducing Endothelial Dysfunction

Cited by 24 publications

References 42 publications

Effects of hyperglycemia on the modulation of vascular function by perivascular adipose tissue

Effects of hyperglycemia on the modulation of vascular function by perivascular adipose tissue

Twenty-five years since the discovery of endothelium-derived relaxing factor (EDRF): does a dysfunctional endothelium contribute to the development of type 2 diabetes?

Acute effects of glucose and insulin on vascular endothelium

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