The displacement of insulin from blood capillaries

Rasio, E

doi:10.1007/bf00427981

Cited by 30 publications

(14 citation statements)

References 13 publications

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“…The minor importance of the peripheral tissues for the disappearance rate of plasma insulin was underlined by the small initial uptake followed by insulin release over the forearm after the insulin challenge in our patients. Displacement of insulin into circulation from capillaries after intravenous insulin administration has been reported previously [13][14][15]. Our results suggest that the low plasma insulin values in response to glucose challenge in patients with arterial insufficiency are due to a decreased pancreatic release and also that these patients have a true increased insulin sensitivity.…”

Section: Discussionsupporting

confidence: 80%

Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency

Hammarsten

Holm

et al. 1980

Eur J Clin Investigation

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Abstract. There have been previous reports of evidence for increased insulin sensitivity in patients with intermittent claudication as the only symptom of arterial insufficiency. This study was designed to evaluate the role of peripheral tissue with respect to insulin sensitivity in such patients. Intravenous glucose tolerance tests (IVGTT) and intravenous insulin tolerance tests (IVITT) were performed in patients with peripheral arterial insufficiency and in controls. During IVGTT the plasma insulin values were significantly lower in patients with arterial insufficiency. During IVITT the venous concentration of glucose decreased more and the area over the glucose curve was significantly larger, suggesting a higher insulin sensitivity in this group. The low insulin values could not be referred to a larger distribution volume or an increased degradation rate, suggesting decreased pancreatic insulin release in this group. At the time of surgery for arterial insufficiency and for varicose veins in controls, the uptake of insulin and glucose and the release of lactate were measured over the leg before and after a glucose load. The uptake of insulin over the leg correlated positively with the arterial insulin concentration and the uptake of glucose in both groups. The insulin uptake had a tendency to be increased in legs with arterial insufficiency during the glucose challenge. The glucose uptake in the leg did not differ in the basal state, but was 3 times higher in the legs of patients with arterial insufficiency during glucose challenge. The increased glucose uptake in this group could be ascribed to a high insulin sensitivity in the leg, as defined by glucose uptake per unit of insulin taken up.

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Section: Discussionsupporting

confidence: 80%

Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency

Hammarsten

Holm

et al. 1980

Eur J Clin Investigation

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“…An early study by Rasio [15], and several subsequent studies [10] [11] demonstrated the interesting phenomena that when observing the disappearance of intravenously injected iodine-labeled insulin, subsequent injection of a large unlabeled insulin bolus not only slowed the disappearance of label (as was seen here) but transiently increased the plasma concentration of iodinated insulin. This did not occur with labeled inulin or albumin[10].…”

Section: Discussionmentioning

confidence: 56%

“…It was suggested that this was due to release of reversibly-bound iodinated insulin from insulin receptors on the endothelial cell. The several previous studies of radioiodinated hindlimb insulin clearance [15] [10, 11] relied on arterial venous differences, direct muscle sampling was not undertaken. Interestingly labeled inulin is reported to enter muscle more rapidly than insulin [10].…”

Section: Discussionmentioning

confidence: 99%

Insulin entry into muscle involves a saturable process in the vascular endothelium

et al. 2011

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Aims/hypothesis Insulin's rate of entry into skeletal muscle appears to be the rate limiting step for muscle insulin action and is slowed by insulin resistance. Despite its obvious importance, uncertainty remains as to whether the transport of insulin from plasma to muscle interstitium is a passive diffusional process or a saturable transport process regulated by the insulin receptor. Methods To address this, here we directly measure the rate of 125I-insulin uptake by rat hindlimb muscle and examine how that is affected by adding unlabeled insulin at high concentrations. We used mono-iodinated ([125I]TyrA14)insulin and short (5 min) exposure times, combined with trichloroacetic acid precipitation, to trace intact bioactive insulin. Results Compared to saline, high concentrations of unlabeled insulin delivered either continuously (insulin clamp) or as a single bolus significantly raised plasma 125I-insulin, slowed the movement of 125I-insulin from plasma into liver, spleen, and heart (p<0.05, for each) but increased kidney 125I-insulin uptake. High concentrations of unlabeled insulin delivered either continuously (insulin clamp), or as a single bolus significantly decreased skeletal muscle 125I-insulin clearance (p<0.01 for each). Increasing muscle perfusion by electrical stimulation did not prevent the inhibitory effect of unlabeled insulin on muscle 125I-insulin clearance. Conclusions/interpretation This indicates that insulin's trans-endothelial movement within muscle is a saturable process likely involving the insulin receptor. Current findings, together with other recent reports, suggest that trans-endothelial insulin transport may be an important site at which muscle insulin action is modulated in clinical and pathologic settings.

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“…Under most physiological conditions the major diffusion barrier to glucose uptake into muscle must be the mus- cle cell membrane. To insulin however, the nonfenestrated (51) capillaries ofskeletal muscle provide a significant diffusion barrier (48,(52)(53)(54)(55) (22,23,58), it is possible that with reduced capillary density there is even a further reduction in insulin at those portions of the muscle cell with least access to a capillary. The correlations of fasting glucose and insulin with capillary density suggest that some direct or indirect factor associated with capillary density must be having an effect on basal glucose homeostasis.…”

Section: Resultsmentioning

confidence: 99%

Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.

Lillioja¹,

Young²,

Culter³

et al. 1987

J. Clin. Invest.

722

484

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We have compared the capillary density and muscle fiber type of musculus vastus lateralis with in vivo insulin action determined by the euglycemic clamp (M value) in 23 Caucasians and 41 Pima Indian nondiabetic men. M value was significantly correlated with capillary density (r = 0.63; P < 0.0001), percent type I fibers (r = 0.29; P < 0.02), and percent type 2B fibers (r = -0.38; P < 0.003). Fasting plasma glucose and insulin concentrations were significantly negatively correlated with capillary density (r = -0.46, P . 0.0001; r = -0.47, P . 0.0001, respectively). Waist circumference/thigh circumference ratio was correlated with percent type 1 fibers (r = -039; P < 0.002). These results suggest that diffusion distance from capillary to muscle cells or some associated biochemical change, and fiber type, could play a role in determining in vivo insulin action. The association of muscle fiber type with body fat distribution may indicate that central obesity is only one aspect of a more generalized metabolic syndrome. The data may provide at least a partial explanation for the insulin resistance associated with obesity and for the altered kinetics of insulin action in the obese.

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The displacement of insulin from blood capillaries

Cited by 30 publications

References 13 publications

Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency

Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency

Insulin entry into muscle involves a saturable process in the vascular endothelium

Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.

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