Preserved Relative Dispersion but Blunted Stimulation of Mean Flow, Absolute Dispersion, and Blood Volume by Insulin in Skeletal Muscle of Patients With Essential Hypertension

Laine, Hanna; Knuuti, Juhani; Ruotsalainen, Ulla; Utriainen, Tapio; Oikonen, Vesa; Raitakari, Maria; Luotolahti, Matti; Kirvelä, Olli; Vicini, Paolo; Cobelli, Claudio; Nuutila, Pirjo; Yki‐Järvinen, Hannele

doi:10.1161/01.cir.97.21.2146

Cited by 28 publications

(21 citation statements)

References 68 publications

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“…Using a very different approach-PET scanning after inhalation of labeled CO-Raitakari et al (47) measured leg muscle blood volume before and during systemic insulin infusion (5 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) in healthy volunteers and later in type 1 diabetic patients (12) and hypertensive subjects (48). The supraphysiologic insulin levels resulted in large increases in total leg blood flow and small (ϳ10%) but significant increases in blood volume.…”

Section: Discussionmentioning

confidence: 99%

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

et al. 2001

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Despite intensive study, the relation between insulin's action on blood flow and glucose metabolism remains unclear. Insulin-induced changes in microvascular perfusion, independent from effects on total blood flow, could be an important variable contributing to insulin's metabolic action. We hypothesized that modest, physiologic increments in plasma insulin concentration alter microvascular perfusion in human skeletal muscle and that these changes can be assessed using contrastenhanced ultrasound (CEU), a validated method for quantifying flow by measurement of microvascular blood volume (MBV) and microvascular flow velocity (MFV). In the first protocol, 10 healthy, fasting adults received insulin (0.05 mU ⅐ kg ؊1 ⅐ min ؊1 ) via a brachial artery for 4 h under euglycemic conditions. At baseline and after insulin infusion, MBV and MFV were measured by CEU during continuous intravenous infusion of albumin microbubbles with intermittent harmonic ultrasound imaging of the forearm deep flexor muscles. In the second protocol, 17 healthy, fasting adults received a 4-h infusion of either insulin (0.1 mU ⅐ kg ؊1 ⅐ min ؊1 , n ‫؍‬ 9) or saline (n ‫؍‬ 8) via a brachial artery. Microvascular volume was assessed in these subjects by an alternate CEU technique using an intra-arterial bolus injection of albumin microbubbles at baseline and after the 4-h infusion. With both protocols, muscle glucose uptake, plasma insulin concentration, and total blood flow to the forearm were measured at each stage. In protocol 2 subjects, tissue extraction of 1-methylxanthine (1-MX) was measured as an index of perfused capillary volume. Caffeine, which produces 1-MX as a metabolite, was administered to these subjects before the study to raise plasma 1-MX levels.In protocol 1 subjects, insulin increased muscle glucose uptake (180%, P < 0.05) and MBV (54%, P < 0.01) and decreased MFV (؊42%, P ‫؍‬ 0.07) in the absence of significant changes in total forearm blood flow. In protocol 2 subjects, insulin increased glucose uptake (220%, P < 0.01) and microvascular volume (45%, P < 0.05) with an associated moderate increase in total forearm blood flow (P < 0.05). Using forearm 1-MX extraction, we observed a trend, though not significant, toward increasing capillary volume in the insulin-treated subjects. In conclusion, modest physiologic increments in plasma insulin concentration increased microvascular blood volume, indicating altered microvascular perfusion consistent with a mechanism of capillary recruitment. The increases in microvascular (capillary) volume (despite unchanged total blood flow) indicate that the relation between insulin's vascular and metabolic actions cannot be fully understood using measurements of bulk blood flow alone.

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Section: Discussionmentioning

confidence: 99%

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

et al. 2001

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“…We have found only short-term studies, relative to rapid weight loss, reported in the literature. It has been reported that water content, a potential reflection of nutritive blood flow (112,142), was increased after a 15.6-kg weight loss over a 9-wk period, suggesting that improved insulin sensitivity may contribute to improve ATBF (110). Recently, rapid weight loss in healthy obese subjects on very low caloric intake diets induced no modification of ATBF when expressed per gram of mass (181).…”

Section: ·Minmentioning

confidence: 99%

Update on adipose tissue blood flow regulation

Sotorník

Brassard

Martin

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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According to Fick's principle, any metabolic or hormonal exchange through a given tissue depends on the product of the blood flow to that tissue and the arteriovenous difference. The proper function of adipose tissue relies on adequate adipose tissue blood flow (ATBF), which determines the influx and efflux of metabolites as well as regulatory endocrine signals. Adequate functioning of adipose tissue in intermediary metabolism requires finely tuned perfusion. Because metabolic and vascular processes are so tightly interconnected, any disruption in one will necessarily impact the other. Although altered ATBF is one consequence of expanding fat tissue, it may also aggravate the negative impacts of obesity on the body's metabolic milieu. This review attempts to summarize the current state of knowledge on adipose tissue vascular bed behavior under physiological conditions and the various factors that contribute to its regulation as well as the possible participation of altered ATBF in the pathophysiology of metabolic syndrome. obesity; insulin; sympathetic nervous system; nitric oxide; angiotensin II; atrial natriuretic peptide; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide OVER THE LAST DECADES, THE WORLDWIDE PANDEMIC of obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM) (188) has attracted ever-increasing attention to the role and significance of adipose tissue (AT). Originally regarded as a mere energy store with insulation and protective cushioning functions, AT is now recognized as a bona fide and highly active metabolic and endocrine organ (102). It has also become evident that the white AT is a heterogeneous tissue. From a metabolic point of view, AT can be subdivided into central (abdominal) and peripheral (hips and buttocks) depots (78). Although extra-abdominal fat accumulation does not bring upon higher metabolic and cardiovascular risk, some reports show a protective influence (124). Conversely, a negative metabolic effect has been associated with central fat (102), which in fact comprises two distinct masses (visceral and subcutaneous) with different metabolic and hormonal activities and impacts on metabolic syndrome pathogenesis (95) and blood flow rates (102).Metabolic processes in fatty tissue require adequate substrate(s) and humoral factor delivery (76). Conversely, adipocytes communicate with other metabolically active tissues through humoral factors (128) as well as through metabolic products (118) serving as energetic substrates. Humoral factors derived from AT arise not only from adipocytes themselves but also from other components of AT such as macrophages and endothelial cells. Moreover, AT is a known conversion site for several hormones or humoral factors, e.g., steroid hormones (156) or components of the renin-angiotensin-aldosterone system (RAAS). All of these functions of AT are tightly linked to the pattern of blood supply and its regulation, which largely differ from other metabolically active organs such as the liver or skeletal muscle (141).In add...

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“…This notion is supported by the significant relationship between changes in IMV and ⌬GDR. The idea that coupling exists between insulin's vascular and metabolic actions is also underscored by the observation that IMV is impaired under conditions of IR as diverse as hypertension (32,33), polycystic ovary syndrome (34), obesity (18), or type 2 diabetes (5). Our findings contrast with those of Vollenweider et al (13) who measured the effect of FFA elevation on IMV in the calf.…”

Section: Fig 2 Effect Of Short-term (A) and Long-term Elevation (B)mentioning

confidence: 99%

Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.

et al. 2000

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The effect and time course of free fatty acid (FFA) elevation on insulin-mediated vasodilation (IMV) and the relationship of FFA elevation to changes in insulin-mediated glucose uptake was studied. Two groups of lean insulin-sensitive subjects underwent euglycemic-hyperinsulinemic (40 mU · m -2 · min -1 ) clamp studies with and without superimposed FFA elevation on 2 occasions ~4 weeks apart. Groups differed only by duration of FFA elevation, either short (2-4 h, n = 12) or long (8 h, n = 7). On both occasions, rates of whole-body glucose uptake were measured, and changes in leg blood flow (LBF) and femoral vein nitric oxide nitrite plus nitrate (NOx) flux in response to the clamps were determined. Short FFA infusion did not have any significant effect on the parameters of interest. In contrast, long FFA infusion decreased rates of whole-body glucose uptake from 47.7 ± 2.8 to 32.2 ± 0.6 µmol · kg -1 · min -1 (P < 0.01), insulin-mediated increases in LBF from 66 ± 8 to 37 ± 7% (P < 0.05), and insulin-induced increases in NOx flux from 25 ± 9 to 5 ± 9% (P < 0.05). Importantly, throughout all groups, FFAinduced changes in whole-body glucose uptake correlated significantly with FFA-induced changes in insulin-mediated increases in LBF (r = 0.706, P < 0.001), which indicates coupling of metabolic and vascular effects. In a different protocol, short FFA elevation blunted the LBF response to N G -monomethyl-L-arginine (L-NMMA), which is an inhibitor of NO synthase. LBF in response to L-NMMA decreased by 17.3 ± 2.4 and 9.0 ± 1.4% in the groups without and with FFA elevation, respectively (P < 0.05), which indicates that FFA elevation interferes with shear stress-induced NO production. Thus, impairment of shear stress-induced vasodilation and IMV by FFA elevation occurs with different time courses, and impairment of IMV occurs only if glucose metabolism is concomitantly reduced. These findings suggest that NO production in response to the different stimuli may be mediated via different signaling pathways. FFA-induced reduction in NO production may contribute to the higher incidence of hypertension and macrovascular disease in insulin-resistant patients.

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Preserved Relative Dispersion but Blunted Stimulation of Mean Flow, Absolute Dispersion, and Blood Volume by Insulin in Skeletal Muscle of Patients With Essential Hypertension

Cited by 28 publications

References 68 publications

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

Physiologic Hyperinsulinemia Enhances Human Skeletal Muscle Perfusion by Capillary Recruitment

Update on adipose tissue blood flow regulation

Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide production.

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