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

Eggleston, Emma M.; Jahn, Linda; Barrett, Eugene J.

doi:10.2337/db07-0670

Cited by 82 publications

(105 citation statements)

References 50 publications

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“…In response to both exercise and insulin, GLUT4 translocation to the muscle membrane is accelerated (21,74), while the ability to phosphorylate glucose may be unaffected or inhibited by G6P. In addition to the effects on glucose transport, exercise and insulin increase muscle capillary blood flow (12,20,44,87). Together these cellular events predict a shift in the barrier from transport to phosphorylation.…”

Section: Distributed Control Of Blood Glucose Removalmentioning

confidence: 99%

Four grams of glucose

Wasserman¹

2009

American Journal of Physiology-Endocrinology and Metabolism

331

264

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Four grams of glucose circulates in the blood of a person weighing 70 kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4 g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated. The body has a remarkable capacity to satisfy the nutritional need for glucose, while still maintaining blood glucose homeostasis. The essential role of glucagon and insulin and the importance of distributed control of glucose fluxes are highlighted in this review. With regard to the latter, studies are presented that show how regulation of muscle glucose uptake is regulated by glucose delivery to muscle, glucose transport into muscle, and glucose phosphorylation within muscle.

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Section: Distributed Control Of Blood Glucose Removalmentioning

confidence: 99%

Four grams of glucose

Wasserman¹

2009

American Journal of Physiology-Endocrinology and Metabolism

331

264

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“…However, as discussed above, even after several hours of hyperinsulinemia, the insulin concentration in the muscle interstitium did not approach plasma concentrations. This would suggest that transport by the endothelium is in fact the limiting process and responsible for the decline in insulin clearance as insulin concentration increases (28).…”

Section: How Does Insulin Exit the Vasculature?mentioning

confidence: 99%

“…We have measured the rate of insulin transport into human forearm skeletal muscle both in the fasting state and during a euglycemic insulin clamp by combining arterial/venous sampling with measurements of forearm blood flow (28). These studies indicated that 10 -15% of the insulin entering muscle with arterial plasma is removed in a single pass at fasting levels of insulin.…”

Section: How Does Insulin Exit the Vasculature?mentioning

confidence: 99%

“…First, we took advantage of the observation made a number of years ago that the uptake of insulin by skeletal muscle could be measured in vivo in humans by using an arterial-venous sampling (49) . We found that, in postabsorptive humans, by using brachial artery and deep forearm vein sampling, the extraction ratio for insulin across the forearm ranged from 10 to 15% (28). After obtaining basal measurements of forearm insulin uptake, we raised plasma insulin concentrations using the euglycemic insulin clamp method.…”

Section: How Does Insulin Exit the Vasculature?mentioning

confidence: 99%

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Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature

Barrett

Wang

Upchurch

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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153

174

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Barrett EJ, Wang H, Upchurch CT, Liu Z. Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am J Physiol Endocrinol Metab 301: E252-E263, 2011. First published May 31, 2011 doi:10.1152/ajpendo.00186.2011Insulin, at physiological concentrations, regulates the volume of microvasculature perfused within skeletal and cardiac muscle. It can also, by relaxing the larger resistance vessels, increase total muscle blood flow. Both of these effects require endothelial cell nitric oxide generation and smooth muscle cell relaxation, and each could increase delivery of insulin and nutrients to muscle. The capillary microvasculature possesses the greatest endothelial surface area of the body. Yet, whether insulin acts on the capillary endothelial cell is not known. Here, we review insulin's actions at each of three levels of the arterial vasculature as well as recent data suggesting that insulin can regulate a vesicular transport system within the endothelial cell. This latter action, if it occurs at the capillary level, could enhance insulin delivery to muscle interstitium and thereby complement insulin's actions on arteriolar endothelium to increase insulin delivery. We also review work that suggests that this action of insulin on vesicle transport depends on endothelial cell nitric oxide generation and that insulin's ability to regulate this vesicular transport system is impaired by inflammatory cytokines that provoke insulin resistance.caveolae; endothelium; microvasculature; insulin transport SEVERAL RELATIVELY RECENT REVIEWS relate to insulin's vascular action. That by Muniyappa et al. (68) focuses particularly on pathways of insulin signaling in both endothelial and smooth muscle cells and how these molecular events explain insulin's vasodilatory action. A review by Clark (21) focuses on insulin as a regulator of nutritive vs. non-nutritive flow and the methodologies that have been developed and applied to skeletal muscle in order to address this role of insulin. We also recently summarized work relating to insulin's vascular action: in particular we focused on the temporal relationship between insulin delivery and insulin-mediated glucose disposal in skeletal muscle, arguing that insulin delivery to muscle is the rate limiting step for insulin action in that tissue (8). Readers are referred to those reviews for a comprehensive discussion of each topic. Here, we will focus first on insulin's vasodilatory effects as they relate to insulin's ability to regulate the delivery of both itself and nutrients to the tissue microvasculature where nutrient exchange occurs. We will then focus on transendothelial insulin movement, as this step appears to be rate limiting for insulin action in skeletal muscle. We will not deal with insulin's direct actions on vascular smooth muscle cells, as this has been well covered in a recent review (2). We will consider the relationship between insulin's effects on skeletal muscle microvascular perfusion and on transendothelial transport as potenti...

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“…Insulin stimulates microvascular recruitment to facilitate delivery of glucose and insulin to the myocyte to enhance glucose disposal [6][7][8][9][10]18]. Insulin resistant rats [3] and obese humans [15,16] also display marked reductions in insulin-mediated microvascular recruitment and insulin-mediated muscle glucose uptake suggesting that the loss of muscle perfusion may contribute to the insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Blueberry Tea Enhances Insulin Sensitivity by Augmenting Insulin-Mediated Metabolic and Microvascular Responses in Skeletal Muscle of High Fat Fed Rats

Bradley²,

Richards³

et al. 2013

IJDVR

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Background: The aim of the current study was to determine whether a unique blueberry tea (BT) ameliorates insulin resistance by improving metabolic and vascular actions of insulin in skeletal muscle. Methods: Male Sprague Dawley rats were fed normal (4.8% fat wt/wt, ND) or high (22.6% fat wt/wt, HFD) fat diets for 4 weeks. A second group of HFD rats was provided BT (4.0% wt/vol) in the drinking water during the final 2 weeks. Animals were subjected to an intraperitoneal glucose tolerance test (1g glucose/kg IPGTT) or euglycaemic hyperinsulinaemic clamp (10mU/min/kg x 2hr). Results: HFD rats displayed significantly (p<0.05) higher plasma glucose levels at 15 and 30 mins following the IPGTT compared to ND, and this increase was completely abolished by BT treatment. Glucose infusion rate, muscle glucose uptake, and microvascular perfusion in muscle were significantly (p<0.05) impaired during clamps in HFD and all markedly improved (p<0.05) with BT treatment. Insulin-mediated changes in femoral artery blood flow were unaffected by HFD or BT treatment. Conclusions: We conclude that BT treatment ameliorates glucose intolerance and insulin resistance by restoring both metabolic and microvascular insulin sensitivity in high fat-fed rats. Therefore, BT consumption may have therapeutic implications for insulin resistance and type 2 diabetes.

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

Cited by 82 publications

References 50 publications

Four grams of glucose

Four grams of glucose

Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature

Blueberry Tea Enhances Insulin Sensitivity by Augmenting Insulin-Mediated Metabolic and Microvascular Responses in Skeletal Muscle of High Fat Fed Rats

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