Transcapillary insulin transfer in human skeletal muscle

Herkner, Harald; Klein, Nikolas; Joukhadar, Christian; Lackner, Edith; Langenberger, Herbert; Frossard, Martin; Bieglmayer, C.; Wagner, Oswald; Roden, Michael; Müller, Markus

doi:10.1046/j.1365-2362.2003.01106.x

Cited by 48 publications

(48 citation statements)

References 27 publications

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“…The potential importance of muscle perfusion for the delivery of insulin to muscle is underscored by studies demonstrating that in muscle, glucose metabolism correlates more strongly with interstitial than with plasma insulin levels (3,4) and by considerable evidence that the transendothelial transport of insulin is rate limiting for its action on muscle glucose metabolism (3,(5)(6)(7). Studies using lymphatic sampling or microdialysis to quantify interstitial insulin concentrations consistently demonstrate 1) a significant time delay between increases in interstitial versus arterial insulin concentrations (3,6,8) and 2) the presence of a persistent (approximately twofold) concentration gradient between interstitial and plasma insulin concentrations both basally (3,9,10) and during steady-state hyperinsulinemia (3,7,9,11).…”

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confidence: 97%

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance

2007

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OBJECTIVE-Transport of insulin from the central circulation into muscle is rate limiting for the stimulation of glucose metabolism. By recruiting muscle microvasculature, insulin may promote its own movement into muscle interstitium. We tested whether in humans, as in the rat, insulin exerts an early action to recruit microvasculature within skeletal muscle. We further hypothesized that expansion of the microvascular volume of muscle would enhance muscle insulin clearance.RESEARCH DESIGN AND METHODS-Microvascular volume, total blood flow, and muscle insulin and glucose uptake (forearm balance method) were measured in 14 lean, healthy volunteers before and during a 2-h hyperinsulinemic-euglycemic clamp (1 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ). Microvascular volume was measured using contrast-enhanced ultrasound.RESULTS-Forearm muscle microvascular volume increased within 20 min of insulin infusion (P Ͻ 0.01), whereas an effect to increase total forearm flow was not observed until 100 min. Forearm insulin uptake increased with physiological hyperinsulinemia (15 Ϯ 3 and 87 Ϯ 13 fmol ⅐ min Ϫ1 ⅐ 100 ml Ϫ1 basal vs. last 40 min of clamp, P Ͻ 0.001). However, the extraction fraction and clearance of insulin declined (P ϭ 0.02, for each), indicating saturability of muscle insulin uptake at physiological hyperinsulinemia.CONCLUSIONS-Skeletal muscle contributes to peripheral insulin clearance both in the basal state and with physiological hyperinsulinemia. Insulin promptly expands human muscle microvascular volume but only slowly increases blood flow. Despite increased microvascular volume available for insulin uptake, muscle insulin clearance decreases significantly. These findings are consistent with the presence of a saturable transport mechanism facilitating the transendothelial transport of insulin into human muscle.

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confidence: 97%

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance

2007

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“…This variability could reflect the inter-patient differences, poor mixing of interstitial fluid, the difficulty of microdialysis techniques or lack of sensitivity to these parameter values. The model fit to data is very good for the Castillo study [9] in the left panel, but less so for the Herkner study [12] in the right panel. The interstitial insulin peak at 15 minutes in the Herkner study does not correspond to any feature in the plasma insulin profile.…”

Section: Sensitivity To Dynamic Parametersmentioning

confidence: 98%

“…The right panel shows the results from method II where each study was weighted equally. Data from the Herkner et al [12] clamp study have been omitted as the minimum error was located at nI = 0, which was not physiologically reasonable. The optimal parameter values vary widely across the 12 data sets, particularly for nI.…”

Section: Sensitivity To Dynamic Parametersmentioning

confidence: 99%

“…Hence, with no plasma insulin peak to create a sharp concentration gradient, the model could not reproduce the reported peak in interstitial insulin, resulting in the poor fit. As noted previously, data from the Herkner et al [12] clamp study were omitted from this analysis. Modelled interstitial insulin profiles did not fit either data set from the Herkner et al [12] study very well.…”

Section: Sensitivity To Dynamic Parametersmentioning

confidence: 99%

“…As noted previously, data from the Herkner et al [12] clamp study were omitted from this analysis. Modelled interstitial insulin profiles did not fit either data set from the Herkner et al [12] study very well. The OGTT example from this study is shown in the right panel of Figure 4.…”

Section: Sensitivity To Dynamic Parametersmentioning

confidence: 99%

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Interstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance

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Penning

et al. 2014

Computer Methods and Programs in Biomedicine

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Glucose-insulin system models are commonly used for identifying insulin sensitivity. With physiological, 2-compartment insulin kinetics models, accurate kinetic parameter values are required for reliable estimates of insulin sensitivity.This study uses data from 6 published microdialysis studies to determine the most appropriate parameter values for the transcapillary diffusion rate (nI) and cellular insulin clearance rate (nC).The 6 studies (12 data sets) used microdialysis techniques to simultaneously obtain interstitial and plasma insulin concentrations. The reported plasma insulin concentrations were used as input and interstitial insulin concentrations were simulated with the interstitial insulin kinetics sub-model. These simulated results were then compared to the reported interstitial measurements and the most appropriate set of parameter values was determined across the 12 data sets by combining the results.Interstitial insulin kinetic parameters values nI = nC = 0.0060 min -1 were shown to be the most appropriate. These parameter values are associated with an effective, interstitial insulin half-life, t½ = 58 minutes, within the range of 25-130 minutes reported by others.

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Microdialysis in Metabolic Research

Jansson

2012

Microdialysis in Drug Development

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Transcapillary insulin transfer in human skeletal muscle

Cited by 48 publications

References 27 publications

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance

Hyperinsulinemia Rapidly Increases Human Muscle Microvascular Perfusion but Fails to Increase Muscle Insulin Clearance

Interstitial insulin kinetic parameters for a 2-compartment insulin model with saturable clearance

Microdialysis in Metabolic Research

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