Insulin-Induced Sympathetic Activation and Vasodilation in Skeletal Muscle: Effects of Insulin Resistance in Lean Subjects

Vollenweider, L; Tappy, Luc; Owlya, Reza; Jéquier, E; Nicod, Pascal; Scherrer, Urs

doi:10.2337/diab.44.6.641

Cited by 60 publications

(18 citation statements)

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“…The approx. 30 % increase in plasma insulin reported in the present study is in agreement with some [8,24,37], but not all [10,38], previous studies.…”

Section: Hormonal Mediationsupporting

confidence: 94%

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

Florian

Pawelczyk

2009

Clinical Science

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Previous studies have shown that acute increases in plasma NEFAs (non-esterified fatty acids) raise SVR (systemic vascular resistance) and BP (blood pressure). However, these studies have failed to distinguish between CNS (central nervous system) mechanisms that raise sympathetic activity and paracrine mechanisms that increase SVR directly, independent of CNS involvement. The aim of the present study was to directly determine whether the sympathetic nervous system contributes to the pressor response to NEFAs. On 2 days separated by at least 2 weeks, 17 lean healthy volunteers (ten male/seven female; age, 22+/-1 years; body mass index, 23+/-1 kg/m2; values are means+/-S.E.M.) received a 4-h intravenous infusion of 20% Intralipid or placebo (in a single-blind randomized balanced order). MSNA (muscle sympathetic nerve activity), HR (heart rate), BP (oscillometric brachial measurement) and Q (cardiac output; acetylene rebreathing) were measured before and throughout infusion. The change in HR (+8.2+/-1.0 and +2.4+/-1.2 beats/min), systolic BP (+14.0+/-1.6 and +3.2+/-2.5 mmHg) and diastolic BP (+8.2+/-1.0 and -0.1+/-1.7 mmHg) were significantly greater after the 4-h infusion of Intralipid compared with placebo (P<0.001). The change in BP with Intralipid resulted from an increase in SVR (Q/mean arterial pressure; P<0.001) compared with baseline, without a change in Q. MSNA burst frequency increased during Intralipid infusion compared with baseline (+4.9+/-1.3 bursts/min; P<0.05), and total MSNA (frequencyxamplitude) was augmented 65% (P<0.001), with no change during placebo infusion. Lipid infusion increased insulin, aldosterone and F2-isoprostane, but not leptin, concentrations. On the basis of the concomitant increase in BP, MSNA and SVR, we conclude that central sympathetic activation contributes to the pressor response to NEFAs.

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“…The approx. 30 % increase in plasma insulin reported in the present study is in agreement with some [8,24,37], but not all [10,38], previous studies.…”

Section: Hormonal Mediationsupporting

confidence: 94%

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

Florian

Pawelczyk

2009

Clinical Science

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“…Thus anesthesia-induced decrease in muscle blood flo w (33) may have led to confounding effects. However, these changes in anesthetized rats are similar in magnitude and in time of onset to those observed for changes caused by insulin in human skeletal muscle (1, [34][35][36][37][38]. These vascular effects of insulin were completely inhibited by ␣-m e t 5 H T administration begun before the insulin clamp.…”

Section: Discussionsupporting

confidence: 59%

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

1999

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Insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle. Studies in perfused rat hindlimb have shown that muscle metabolism can be regulated by vasoactive agents that control blood flow distribution within the hindlimb. In the present study, the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusion distribution in rat hindlimb was investigated in vivo to determine its effects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats. Blood flow distribution within the hindlimb muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1-MX metabolism indicating less capillary flow. Insulin infusion caused decreased hindlimb vascular resistance that was associated with increased femoral blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion commenced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT infusion had no effect on hindlimb glucose uptake but markedly inhibited the insulin stimulation of glucose uptake (P < 0.05) and was associated with decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this kind results from stress-induced increase in sympathetic outflow, then this may provide a clue as to the link between hypertension and insulin resistance that is often observed in humans.

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“…In this study, the increase in FBF occurred a few hours before the increase in insulin level was observed. Insulin induces a dose-and time-dependent vasodilation in the peripheral arteries by an endothelium-dependent mechanism including the L-arginine-nitric oxide pathway and the sympathetic nervous system (Utriainen et al 1995;Vollenweider et al 1995). Insulin-mediated vasodilation requires insulin levels in the range of 50-70 lU.ml -1 , this does not occur at levels below 10 lU.ml -1 (Anderson et al 1991;Hausberg et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Sustained hyperglycaemia increases muscle blood flow but does not affect sympathetic activity in resting humans

et al. 2004

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An increase in capillary blood flow and pressure in response to diabetes mellitus may lead to microangiopathy. We hypothesize that these haemodynamic changes are caused by a decreased activity of the sympathetic nervous system due to episodes of sustained hyperglycaemia. Twelve healthy volunteers consecutively underwent a hyperglycaemic experiment (HYPER), with the plasma glucose level maintained at 20 mmol.l(-1) for 6 h by combined infusion of somatostatin, insulin and glucose; and a normoglycaemic experiment (NORMO), with similar infusions but with the plasma glucose maintained at fasting level. During both experiments, sympathetic nervous system (SNS) activity was measured by assessing the plasma catecholamine levels, microneurography, power spectral analysis and forearm blood flow (FBF). In an age- and weight matched group, fasting and 6-h sympathetic activity was measured without infusion of somatostatin and insulin (CONTROL). During HYPER, forearm blood flow increased from 2.45 (0.21) to 3.10 (0.48) ml.dl(-1).min(-1) ( P <0.05), but did not change in NORMO or CONTROL. The HYPER conditions did not change the plasma noradrenaline levels or the muscle sympathetic nerve activity [42 (4), 50 (10) and 45 (5) bursts/100 beats, HYPER, NORMO and CONTROL respectively]. Also, the power spectral analysis was similar under all experimental conditions. All results are expressed as the mean (SEM). In conclusion, sustained hyperglycaemia in normal subjects induces moderate vasodilation in skeletal muscle, but this increased blood flow can not be attributed to a decreased sympathetic tone.

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Insulin-Induced Sympathetic Activation and Vasodilation in Skeletal Muscle: Effects of Insulin Resistance in Lean Subjects

Cited by 60 publications

References 0 publications

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

Non-esterified fatty acids increase arterial pressure via central sympathetic activation in humans

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Sustained hyperglycaemia increases muscle blood flow but does not affect sympathetic activity in resting humans

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