Impaired Delivery of Insulin to Adipose Tissue and Skeletal Muscle in Obese Women with Postprandial Hyperglycemia

Sandqvist, Madeléne; Strindberg, Lena; Schmelz, Martin; Lönnroth, Peter; Jansson, Per‐Anders

doi:10.1210/jc.2011-0233

Cited by 34 publications

(31 citation statements)

References 20 publications

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“…Several studies have shown impaired access of insulin to skeletal muscle in obese humans (38,41), yet a recent study using lipid infusion to induce insulin resistance observed no reduction in the transport of insulin across the vessel wall (45). However, this human study did not report actual levels of interstitial insulin but instead reported change from basal.…”

mentioning

confidence: 73%

“…We confirmed that there was no change in the time to steady state but also that the insulin concentration in the lymph (as a measure of the interstitial fluid) was not different from healthy animals. In contrast, long-term physiological models of human insulin resistance do show impaired insulin access (41), and obese patients with postprandial hyperglycemia require a higher level of insulin in the plasma to attain similar interstitial insulin levels as those in healthy patients (38). Thus, it is possible that insulin clearance rates in models of insulin resistance are altered to keep the supply of insulin to muscle and other insulin-sensitive tissues at an optimum level.…”

Section: Discussionmentioning

confidence: 99%

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Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Kolka

Richey

Castro

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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mentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Kolka

Richey

Castro

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…In obese, non-pregnant individuals, delayed insulin absorption has been associated with large insulin doses and reduced subcutaneous adipose tissue blood flow [31,32]. Sandqvist et al reported impaired transport of insulin from the circulation to both adipose tissue and muscle in obese, insulin-resistant postmenopausal women [33]. Although the distribution of insulin to adipose tissue correlated with factors relevant to insulin resistance, the metabolic impact of impaired insulin delivery was unclear.…”

Section: Discussionmentioning

confidence: 99%

Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy

et al. 2011

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Aims/hypothesis Although maternal hyperglycaemia is associated with increased risk of adverse pregnancy outcome, the mechanisms of postprandial hyperglycaemia during pregnancy are poorly understood. We aimed to describe glucose turnover in pregnant women with type 1 diabetes, according to stage of gestation (early vs late gestation). Methods The rates of systemic glucose appearance (R a ) and glucose disposal (R d ) were measured in ten pregnant women with type 1 diabetes during early (12-16 weeks) and late (28-32 weeks) gestation. Women ate standardised meals-a starch-rich 80 g carbohydrate dinner and a sugarrich 60 g carbohydrate breakfast-and fasted between meals and overnight. Stable-label isotope tracers ([6,6-2 H 2 ]glucose and [U-13 C]glucose) were used to determine R a , R d and glucose bioavailability. Closed-loop insulin delivery maintained stable glycaemic conditions. Results There were no changes in fasting R a (10±2 vs 11±2 μmol kg -1 min -1 ; p=0.32) or fasting R d (11±2 vs 11±1 μmol kg -1 min -1 ; p=0.77) in early vs late gestation. There was increased hepatic insulin resistance (381±237 vs 540 ± 242 μmol kg -1 min -1 × pmol/l; p = 0.04) and decreased peripheral insulin sensitivity (0.09±0.04 vs 0.05±0.02 μmol kg -1 min -1 per pmol/l dinner, 0.11±0.05 vs 0.07±0.03 μmol kg -1 min -1 per pmol/l breakfast; p=0.002) in late gestation. It also took longer for insulin levels to reach maximal concentrations (49 [37-55]

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“…However, there is a lack of data clarifying whether insulin regulates that transport or whether a transendothelial insulin concentration gradient is present in adipose tissue and whether insulin TET limits insulin action in adipose tissue (96).…”

Section: Nutrient and Hormone Transfer Across The Endotheliummentioning

confidence: 99%

Muscle microvasculature's structural and functional specializations facilitate muscle metabolism

Kusters

Barrett

2016

American Journal of Physiology-Endocrinology and Metabolism

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Kusters YH, Barrett EJ. Muscle microvasculature's structural and functional specializations facilitate muscle metabolism. Am J Physiol Endocrinol Metab 310: E379-E387, 2016. First published December 29, 2015; doi:10.1152/ajpendo.00443.2015.-We review the evolving findings from studies that examine the relationship between the structural and functional properties of skeletal muscle's vasculature and muscle metabolism. Unique aspects of the organization of the muscle microvasculature are highlighted. We discuss the role of vasomotion at the microscopic level and of flowmotion at the tissue level as modulators of perfusion distribution in muscle. We then consider in some detail how insulin and exercise each modulate muscle perfusion at both the microvascular and whole tissue level. The central role of the vascular endothelial cell in modulating both perfusion and transendothelial insulin and nutrient transport is also reviewed. The relationship between muscle metabolic insulin resistance and the vascular action of insulin in muscle continues to indicate an important role for the microvasculature as a target for insulin action and that impairing insulin's microvascular action significantly affects body glucose metabolism. muscle microvasculature; vasomotion; flowmotion; endothelium; insulin resistance MUSCLE'S MICROVASCULATURE IS THE FINAL INTERFACE through which circulating nutrients, hormones, gases, and electrolytes must pass in journeying to and from the systemic circulation. It has evolved multiple structural and functional adaptations to flexibly and efficiently fulfill its role in optimizing muscle function. Here, we examine how the minute-to-minute metabolic activity of skeletal muscle is coupled to the function of muscle's vasculature. We will discuss how bulk blood flow and flow distribution can regulate nutrient delivery to muscle microvasculature as well as how transendothelial transport processes can modulate the exchange of hormones and metabolites between plasma and the myocytes. We focus on acute regulatory relationships and defer discussion of chronic vascular or myocyte adaptation to environmental, nutritional, and most pathological processes.Muscle blood flow has been measured in numerous classical limb balance and metabolic tracer studies of the acute effects of fasting, feeding, exercise, and hormonal manipulation on muscle nutrient exchange. These methods, however, treat muscle's vasculature as a "black box." Here, we consider muscle microvasculature's specialized architecture and how that architecture might impact nutrient fluxes into and out of the muscle. We will discuss the role of vasomotion and flowmotion in the regulation of microvascular perfusion. We recognize that factors acting on the endothelial cell (EC), the vascular smooth muscle cell (SMC), or pericytes may affect muscle perfusion.We will consider in more detail the effect insulin and exercise have on the endothelium and directly or indirectly on the vascular SMC to influence nutrient delivery.Beyond muscle perfusion, we will co...

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Impaired Delivery of Insulin to Adipose Tissue and Skeletal Muscle in Obese Women with Postprandial Hyperglycemia

Abstract: Obese subjects with postprandial hyperglycemia need higher circulating insulin levels than lean controls to attain similar interstitial insulin levels in adipose tissue and skeletal muscle, indicating an impaired transfer of insulin across the endothelium.

Cited by 34 publications

References 20 publications

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

Pathophysiology of postprandial hyperglycaemia in women with type 1 diabetes during pregnancy

Muscle microvasculature's structural and functional specializations facilitate muscle metabolism

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