Hyperglycaemia modifies the reaction of microvessels to insulin in rat skeletal muscle

Renaudin, C; Michoud, E.; Rapin, J. R.; Lagarde, Michel; Wiernsperger, Nicolas

doi:10.1007/s001250050862

Cited by 47 publications

(59 citation statements)

References 54 publications

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“…One has looked at the chronological evolution of the process in insulin-resistant, fructose-fed rats and found that they were first insulin resistant, then endothelium-dependent vasodilatation defects appeared and finally hypertension developed [14]. Precapillary vasomotion was impaired in our study in the muscle of such rats after acute hyperglycaemia [15,16]. The myogenic response was impaired in non-diabetic, galactosefed rats [17].…”

Section: Functional Changesmentioning

confidence: 63%

Defects in microvascular haemodynamics during prediabetes: contributor or epiphenomenon?

Wiernsperger

2000

Diabetologia

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Although diabetes is frequently characterized by microangiopathy, evidence accumulated over recent years suggests that most of these defects can be detected well before fasting hyperglycaemia is present. As will be explained, this observation applies even to prediabetic states that are not linked to defects in glucose tolerance, thereby suggesting that insulin resistance (or hyperinsulinaemia or both) are more causal than glycaemic control.If so, the microcirculatory abnormalities have to be linked to both causal processes and possible consequences. The heterogeneity of the insulin-resistance state, which makes comparisons between patient groups questionable, and the technical difficulties inherent in researching microcirculation in relevant tissues are largely responsible for our lack of knowledge in this field. Nevertheless in this paper I examine possible hypotheses about origins and potential meaning of disturbances in microvascular haemodynamics during prediabetes.

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Section: Functional Changesmentioning

confidence: 63%

Defects in microvascular haemodynamics during prediabetes: contributor or epiphenomenon?

Wiernsperger

2000

Diabetologia

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“…at 5 mmol/l [18]) instead of at isoglycaemia, which resulted in slightly higher glucose levels during insulin than during saline infusion. It is not clear whether this difference affected our results, but because hyperglycaemia impairs microvascular function [47,48], we may, if anything, have somewhat underestimated insulin-mediated effects on microvascular function.…”

Section: Discussionmentioning

confidence: 86%

Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers

et al. 2004

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Aims/hypothesis. Insulin possesses vasodilatory actions that may be important in regulating its access to insulin-sensitive tissues. Our study aims to directly measure changes in response to insulin in the human skeletal muscle microcirculation. Measurement was by an implanted laser Doppler probe. Methods. We investigated changes in intramuscular and skin microvascular perfusion in 12 healthy individuals during a hyperinsulinaemic and a control clamp. We determined leg blood flow with plethysmography, finger skin functional capillary recruitment with capillaroscopy, endothelium-(in)dependent vasodilation by iontophoresis of acetylcholine and sodium nitroprusside, and leg intramuscular reactive hyperaemia and vasomotion with laser Doppler measurements. Results. Compared to the control study, hyperinsulinaemia (416±82 pmol/l) caused: (i) an increase in leg blood flow (1.0±1.0 vs 0.1±0.6 ml·min −1 ·100 ml, p<0.05); (ii) an increase in finger skin capillary recruitment (14.9±10.1 vs -5.6±11.0%, p<0.01); (iii) no change in baseline laser Doppler perfusion either in finger skin or leg muscle; (iv) a tendency to increase acetylcholine-mediated vasodilation (475±534 vs 114±337%, p=0.07) with no change in sodiumnitroprusside-mediated vasodilation (p=0.2) in finger skin; (v) an increase in intramuscular reactive hyperaemia (423±507 vs 0±220%, p<0.01); and (vi) a decrease in time needed to reach peak intramuscular perfusion (−3.6±3.0 vs 1.1±3.1 s, p<0.01). In addition, hyperinsulinaemia induced an increase in intramuscular vasomotion by increasing the contribution of frequencies between 0.01 and 0.04 Hz (p<0.05 for all), which probably represents increased endothelial and neurogenic activity. Conclusions/interpretation. Physiological hyperinsulinaemia not only stimulates total blood flow and skin microvascular perfusion, but also augments human skeletal muscle microvascular recruitment and vasomotion as detected directly by laser Doppler measurements.

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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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Hyperglycaemia modifies the reaction of microvessels to insulin in rat skeletal muscle

Cited by 47 publications

References 54 publications

Defects in microvascular haemodynamics during prediabetes: contributor or epiphenomenon?

Defects in microvascular haemodynamics during prediabetes: contributor or epiphenomenon?

Physiological hyperinsulinaemia increases intramuscular microvascular reactive hyperaemia and vasomotion in healthy volunteers

Acute effects of glucose and insulin on vascular endothelium

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