Intra-arterial infusion of insulin attenuates vasoreactivity in human forearm.

Sakai, Kotaro; Imaizumi, Tsutomu; Masaki, Hiroyuki; Takeshita, Akira

doi:10.1161/01.hyp.22.1.67

Cited by 68 publications

(46 citation statements)

References 29 publications

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“…The stimulation of 45Ca2' efflux by 5-HT was expected because 5-HT stimulates Ca2' release from intracellular stores (Fig 1, bottom). The finding that insulin had no effect on 45Ca2' efflux indicates that insulin does not stimulate sarcolemmal Ca2' efflux and thus supports the data in Fig 1. To determine the effects of insulin on the release of Ca2' from intracellular stores, we studied saponinskinned cells.23 24 To verify that saponin effectively increased sarcolemmal Ca2' permeability in these cells, the uptake of 45Ca21 was assayed by cells that had been preincubated with or without 20 ,g/mL saponin for 5 minutes. As shown in Fig 4, saponin increased 45Ca2+ uptake, indicating that this agent increased sarcolemmal Ca24 permeability or increased Ca2' binding by the sarcolemma and/or intracellular sites.…”

Section: Methodsmentioning

confidence: 99%

Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.

Kahn¹,

Allen²,

Seidel³

et al. 1994

Circulation

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BACKGROUND Insulin in physiological concentrations attenuates the agonist-induced intracellular Ca2+ ([Ca2+]i) transient and inhibits contraction in individual nonproliferated cultured canine femoral artery vascular smooth muscle cells (VSMCs). In the present study, we wished to define the effects of insulin on individual components of Ca2+ transport in vascular smooth muscle. METHODS AND RESULTS Insulin (40 microU/mL) attenuated the 5-hydroxytryptamine (5-HT, serotonin; 10(-5) mol/L)-induced [Ca2+]i transient (measured by fura 2 fluorescence) in primary confluent canine femoral artery VSMCs in the presence of extracellular Ca2+. In Ca(2+)-free media, the 5-HT-induced [Ca2+]i transient was reduced by 42% and was not affected by insulin. This finding suggested that insulin inhibits 5-HT-induced Ca2+ influx but does not affect sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores. In support of those conclusions, we found that insulin inhibited the 5-HT-induced component of Mn2+ (a Ca2+ surrogate) influx (measured by fura 2 fluorescence quenching at the Ca2+ isosbestic excitation wavelength). In addition, 5-HT stimulated the rates of 45Ca2+ efflux from intact cells (a measure of sarcolemmal Ca2+ efflux) and from saponin-permeabilized cells (a measure of Ca2+ release from intracellular stores), but insulin did not affect these rates of 45Ca2+ efflux. CONCLUSIONS We conclude that a physiological insulin concentration attenuates the 5-HT-induced [Ca2+]i transient in confluent primary cultured canine femoral artery VSMCs by inhibiting the 5-HT-induced component of Ca2+ influx but not by affecting sarcolemmal Ca2+ efflux or Ca2+ release from intracellular stores.

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Section: Methodsmentioning

confidence: 99%

Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.

Kahn¹,

Allen²,

Seidel³

et al. 1994

Circulation

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“…Whereas some authors have found an increase in blood flow in response to local insulin administration [6,7], others have not [8][9][10]. Based on the latter findings it has been concluded that the insulin-induced vasodilatation is centrally mediated [11,12].…”

Section: Introductionmentioning

confidence: 99%

Direct vasodilator effects of physiological hyperinsulin‐aemia in human skeletal muscle

Tack

Schefman

Willems³

et al. 1996

Eur J Clin Investigation

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Abstract. Systemic hyperinsulinaemia induces vasodi latation in human skeletal muscle. This effect is gra dual in onset, and at low insulin levels not maximal until at least 3 h. To investigate whether the vasodi lator response to insulin results from a direct vascular effect, we infused insulin directly into the cannulated brachial artery (perfused forearm technique) in a total of 30 experiments in 20 healthy, lean, normotensive volunteers. Local, intra-arterial, infusion of insulin (180 min, O O m U dL " 1 forearm volumemin" 1, « = 15, forearm venous insulin concentration approximately 540pm olL -1) induced a gradual increase in forearm blood flow (FBF; venous occlusion plethysmography) from 1-86 ± 0*17 to 3*64 ± 0,6 4 m L d L " 1 min~l after 180 min (a n o v a P < 0-001), Percentage increases in FBF after 60, 120 and 180 min averaged 14*4 ± 5-9, 59*4 ± 25*5 and 124*6 ± 51*2% respectively. Fore arm glucose uptake increased from 0*24 ± 0-05 to a maximum of 1*98 ± 0-28 /.¿moldL~l min (P < 0 001). Furthermore, insulin infusion increased forearm lac tate release and potassium uptake. In 10 out of these 15 individuals, the forearm glucose uptake was further increased in a second, separate, repeat experiment with concomitant intra-arterial infusion of glucose 5% (O^mLdL™ 1 m in-1), resulting in forearm venous glucose concentrations of approximately 15 mmol L"*1. This combined infusion achieved a simi lar vasodilator response to the infusion of insulin alone. The individual vascular responses of the two paired experiments showed a strong correlation (r = 0*87, P < 0*01). In five subjects time and vehicle control experiments were performed, showing no changes in FB F or metabolism during the 180 min. W e conclude that the slow vasodilator response to insulin (as observed during systemic infusion) can, at least partly, be explained by a direct vascular effect of insulin. Insulin-mediated skeletal muscle glucose uptake precedes this effect, but seems not to be an im portant determinant of the vasodilator response to insulin.

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“…Moreover, acute increases in plasma insulin within the physiological range have shown conflicting responses in forearm vasodilation [21,22], but with no increase in blood pressure despite increased sympathetic neural outflow [21] and a marked increase in forearm noradrenaline release [22]. Local hyperinsulinaemia (using a brachial artery infusion) attenuates neurogenic vasoconstriction induced by lower body negative pressure [23] and also the pharmacological vasoconstriction of phenylephrine and angiotensin II [24]. Most studies have shown no changes in baseline forearm vascular resistance detected during intra-arterial insulin infusion [23][24][25][26] suggesting that a direct vasodilatory effect of insulin is unlikely.…”

mentioning

confidence: 99%

“…Local hyperinsulinaemia (using a brachial artery infusion) attenuates neurogenic vasoconstriction induced by lower body negative pressure [23] and also the pharmacological vasoconstriction of phenylephrine and angiotensin II [24]. Most studies have shown no changes in baseline forearm vascular resistance detected during intra-arterial insulin infusion [23][24][25][26] suggesting that a direct vasodilatory effect of insulin is unlikely.…”

mentioning

confidence: 99%

The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers

et al. 1995

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Summary Impaired reactivity of the resistance vasculature may contribute to the development of diabetic microangiopathy by altering microvascular haemodynamics. This study investigates the acute effects of insulin on the contractility and relaxation properties of isolated human resistance arteries (< 300 ~tm internal diameter) taken from gluteal subcutaneous fat of 33 (18 male: 15 female) normotensive healthy volunteers (supine blood pressure 115.6 + 1.6/ 70.0 + 1.5 mmHg [mean + SEM], with no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after incubation in 1 mU/ml of insulin for 20 min (p < 0.01; Group 1). Increasing concentrations of insulin were found to reduce the contractile response to noradrenaline in a dose-dependent manner (Group2; 0.1mU/ml by 8% [p

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Intra-arterial infusion of insulin attenuates vasoreactivity in human forearm.

Cited by 68 publications

References 29 publications

Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.

Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle.

Direct vasodilator effects of physiological hyperinsulin‐aemia in human skeletal muscle

The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers

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