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Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension.
Open accessAbstract
The reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/kg per min) while maintaining euglycemia. Hyperinsulinemia (50-60 microU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28 +/- 45 ng.liter-1.min-1 in hypertensives and 0.80 +/- 0.27 ng.liter-1 in normals; P less than 0.01). Forearm glucose uptake rose to 5.1 +/- .7 mg.liter-1.min-1 in response to insulin in hypertensives and to 7.9 +/- 1.3 mg.liter-1.min-1 in normotensives (P less than 0.05). To clarify whether insulin action was due to a direct effect on muscle NE metabolism, in another set of experiments insulin was infused locally into the brachial artery to expose only the forearm tissues to the same insulin levels as in the systemic studies. During local hyperinsulinemia, forearm NE release remained virtually unchanged both in hypertensive and in normal subjects. Furthermore, forearm glucose disposal was activated to a similar extent in both groups (5.0 +/- 0.6 and 5.2 +/- 1.1 mg.liter-1.min-1 in hypertensives and in normals, respectively). These data demonstrate that: (a) insulin evokes an abnormal muscle sympathetic overactivity in essential hypertension which is mediated by mechanisms involving the central nervous system; and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity. The data fit the hypothesis that the sympathetic system mediates the pathophysiologic link between hyperinsulinemia and essential hypertension.
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TL;DR
In patients with essential hypertension, systemic euglycemic hyperinsulinemia evoked a threefold greater increase in forearm skeletal muscle norepinephrine release than in normotensive controls. Local intra-arterial insulin did not change norepinephrine release in either group, suggesting the abnormal sympathetic response is centrally mediated rather than a direct muscle effect.
Key findings
- Systemic insulin infusion increased forearm NE release in both groups, but the absolute rise was threefold higher in hypertensives (2.28±0.45 vs. 0.80±0.27 ng·liter⁻¹·min⁻¹; P < 0.01); percent increases were 140% in hypertensives (P < 0.001) and 35% in normotensives (P < 0.05).
- During systemic insulin, forearm glucose uptake was lower in hypertensives than normotensives (5.1±0.7 vs. 7.9±1.3 mg·liter⁻¹·min⁻¹; P < 0.05), and whole-body glucose utilization was also lower (4.6±0.3 vs. 5.8±0.5 mg/kg per min; P < 0.05).
- During local intrabrachial insulin, forearm NE release remained virtually unchanged in both groups, while forearm glucose disposal was similar in hypertensives and normals (5.0±0.6 and 5.2±1.1 mg·liter⁻¹·min⁻¹, respectively).
- Forearm NE balance increased fourfold in hypertensives during systemic hyperinsulinemia (P < 0.05), whereas it was statistically indistinguishable from zero in normals.
Methods
- Forearm perfusion technique with tritiated norepinephrine tracer was used in 45 subjects: 21 normotensives and 24 patients with mild to moderate essential hypertension.
- Two protocols: systemic insulin infusion at 1 mU/kg per min for 120 min with euglycemia (12 normals, 14 hypertensives), or local intrabrachial insulin at 0.05 mU/kg per min (9 normals, 10 hypertensives); tracer subgroups received [³H]norepinephrine.
- Forearm NE kinetics were calculated from arterial–venous balance, fractional extraction, clearance, uptake, and release; comparisons used paired and unpaired t tests, with values reported as mean±SE.
Limitations
- The paper states that it cannot answer whether hyperinsulinemia is the primary defect leading to hypertension via sympathetic overactivity, and that an alternative primary sympathetic overactivity causing both hypertension and insulin resistance would be equally compatible with the data.
- The paper states that the mechanism of insulin-evoked muscle sympathetic overactivity is unknown and that a peripheral reflex such as a venous baroreflex or chemoreflex cannot be excluded.
- Evident from the text: sample sizes are small, especially for tracer subgroups (e.g., 8 normals and 7 hypertensives for systemic tracer studies; 5 and 5 for local tracer studies), and the local infusion model relies on adequate mixing, which was assessed in only 16 tested cases.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Hyperinsulinemia (50-60 jsU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Forearm glucose uptake increased in response to intraarterial insulin infusion to a comparable ex- tent in both groups.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean absolute change in forearm NE release during hyperinsulinemia was threefold higher in hypertensive (2.28±0.45ng.liter-' * min') than in normotensive subjects (0.80±0.27 ng liter-' * min-') (P < 0.01) (Fig. 1).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Arterial plasma FFA levels were not affected by local insulin (from 0.42±0.05 to 0.39±0.04mmol in normal sub- jects and from 0.36±0.05 to 0.39±0.05mmol in hypertensives).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“since blood pressure remained unchanged throughout insulin infusion.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During local hyperinsulinemia, forearm NE release re- mained virtually unchanged both in hypertensive and in normal subjects.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Comparable values of NE fractional extraction and clearance were found during both the basal state and the hyperinsulin- emic period.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and did not change significantly during insu- lin infusion in both groups (Table II).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Arterial blood glucose levels remained unchanged in both groups during local, intrabrachial insulin infusion.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“During the hyperinsuline- mic period, forearm NE release increased significantly by 35% in normotensives (P < 0.05).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 17
- Probably not a substantial claim. 8
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heart rate was comparable in the two groups in basal conditions and increased slightly during hyperinsulinemia only in hypertensive patients (P < 0.05).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In normal subjects, forearm NE balance was statistically indistinguishable from zero both in the basal state and during insulin infusion.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As expected, systolic and diastolic blood pressures were significantly higher in hypertensives than in normotensives”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both forearm NE uptake and NE release were totally unaffected by local forearm insulinization.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma insulin concentration in the deep forearm vein was similar in the basal state in the two groups and increased to a comparable extent during systemic insulin infusion.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Accordingly, forearm NE uptake was similar in the basal state and increased comparably in the two groups during insulin infusion (P < 0.05).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Forearm glucose uptake rose to 5.1±.7 mg * liter-' * min-in response to insulin in hypertensives and to 7.9±1.3mg.liter' -min' in normotensives (P < 0.05).”
- Also stated in: § Downers Grove, IL). · plain
“Forearm glucose uptake in the basal state was not statistically different in normal and hypertensive subjects and increased considerably in response to insulin infusion in both groups.However, the levels attained in hypertensive patients were significantly lower than those ob- served in control subjects (P < 0.05) (Table III).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Downers Grove, IL). · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ve- nous plasma insulin levels increased to the same extent after insulin whereas systemic insulin concentration remained stable at its basal level.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in Table III, basal arterial blood glucose concen- trations were similar in normal and hypertensive subjects, and remained virtually unchanged during insulin infusion in both groups.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Estimated forearm blood flow was similar in the two groups in the basal state and increased slightly but not signifi- cantly after insulin administration (Table III).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Downers Grove, IL).
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data demonstrate that: (a) insulin evokes an ab- normal muscle sympathetic overactivity in essential hyperten- sion which is mediated by mechanisms involving the central nervous system;”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In this model, insu- lin resistance, hyperinsulinemia, and hypertension develop”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
What the sources say
- Not checked yetcites [5]
- Not checked yetcites [6]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Particularly relevant is the observation that a program of physical activity or body weight control leads to a parallel reduction of hyperinsulinemia and blood pressure levels (7).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
What the sources say
- Not checked yetcites [7]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This leads to the conclu- sion that all of the insulin effect on muscle NE metabolism, seen with systemic insulinization, is mediated either by central mechanisms involving the hypothalamic nuclei or by a periph- eral reflex.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Forearm norepinephrine release measured by the [3H]norepinephrine infusion technique reflects skeletal muscle sympathetic nerve activity.
In the paper
“Of interest is also the recent observation that in the offspring of essential hyperten- sive parents insulin resistance and hyperinsulinemia are de- monstrable before the development of high blood pressure (8).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
What the sources say
- Not checked yetcites [8]
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“(d) sympathetic overactivity may be potentially responsible for elevated blood pressure (15)”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
What the sources say
- Not checked yetcites [15]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Evi- dence to support this last hypothesis comes from the observa- tion that in vitro insulin affects NE uptake by the atrial strips (39).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
What the sources say
- Not checked yetcites [39]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“and that NE can in- duce vascular smooth muscle cell polyploidy independent of blood pressure elevation (47).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
What the sources say
- Not checked yetcites [47]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Alternatively, the data may indicate that the exaggerated sympathetic activation induced by systemic insulinization in hypertensives may play a causal role in the impaired glucose uptake by the muscle tissue.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These are potential factors that may lead to structural alterations in the arterial vessels, thus reducing the lumen area, amplifying the vasoconstrictor re- sponse to contractile agents, and limiting vasodilation.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whatever the initial event, our data also point out the possibility that the abnormal sympathetic response to insulin may further aggravate insulin resistance and hypennsu- linemia, thus acting as a self-perpetuating mechanism in essen- tial hypertension.”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The different response of muscle glucose uptake to local or systemic insulin may suggest that muscle insulin resistance in hypertension is entirely mediated by the indirect component of insulin action (28).”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
What the sources say
- Not checked yetcites [28]
Tests✗ Asserted: fails✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The authors may not put it forward as true.
None of the sources cited for this claim have been checked yet.
In the paper
“In this context, it is pertinent to recall that the sympa- thetic nervous system promotes the growth of vascular muscle fibers (43, 44) and myocardium (45,46)”
§ Abnormal Sympathetic Overactivity Evoked by Insulin in the Skeletal Muscle of Patients with Essential Hypertension > Discussion
What the sources say
- Not checked yetcites [43]
- Not checked yetcites [44]
- Not checked yetcites [45]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The reason why hyperinsulinemia is associated with essential hypertension is not known.
“The reason why hyperinsulinemia is associated with essential hypertension is not known.”
The paper relies on this without support.
The available clinical data support the concept that insulin and human hypertension must be linked by pathophysiologic mechanisms.
“The available clinical data, however, tend to support the concept that the two factors must be linked by pathophysiologic mechanisms.”
The paper relies on this without support.
The effluent venous blood from the deep antecubital vein drains predominantly muscle tissue.
“Under these conditions, the effluent venous blood drained predominantly muscle tissue.”
The paper relies on this without support.
Forearm norepinephrine release measured by the [3H]norepinephrine infusion technique reflects skeletal muscle sympathetic nerve activity.
“In conclusion, the current study provides evidence for an abnormal muscle sympathetic activity reflexly evoked by insu- lin in essential hypertension.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Euglycemic hyperinsulinemia evokes both sympathetic activation and vasodilation in skeletal muscle, but the mechanism remains unknown.”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [8]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Alternatively, a central neural action of insulin may also contribute to stimulation of sympathetic outflow in this setting (8, 40-43).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [8]
The cited source says what the claim attributes to it.
In the citing paper
“findings in humans, showing that local intraarterial insulin infusion, in contrast to systemic intravenous infusion, did not have any stimulatory effect on sympathetic activity in skeletal muscle (15).”
From Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. (1994) · cites this paper as [15]
The cited source says what the claim attributes to it.
In the citing paper
“in hypertensive insulin-resistant humans, Lembo et al. (15) recently provided evidence for augmented stimulation of norepinephrine release into forearm tissue by insulin.”
From Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. (1994) · cites this paper as Lembo et al. (15)
In the citing paper
“In contrast, Lembo et al84 demonstrated that insulin-induced increases in sympathetic activity and norepinephrine release in skeletal muscle are substantially exaggerated in hypertensive patients (Figure 3, right panel).”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [84]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
NE-release calculation has its subtraction reversed
MinorUnder the paper's stated sign convention, net NE balance is uptake minus release. Release therefore equals uptake minus net balance, not net balance minus uptake as the calculation describes.
“Once FNU was calculated, forearm NE release was easily obtained by subtracting FNU from the net NE balance.”
“Positive or nega- tive balance values indicate uptake or release, respectively.”
Citations
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The Effect of Weight Loss on the Sensitivity of Blood Pressure to Sodium in Obese Adolescents
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Sundell, J., Laine, H. K., Luotolahti, M., Nuutila, P., & Knuuti, J. M. (2002) · Journal of Vascular Research · doi:10.1159/000064520 · Cited by 3
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Metadata
- Authors
- Lembo, G., Napoli, R., Capaldo, B., Rendina, V, Iaccarino, G., Volpe, M., Trimarco, B., & Saccà, L.
- Affiliations
- Federico II University Hospital (IT)
- Venue
- Journal of Clinical Investigation
- Published
- 1992-07-01
- Volume
- 90
- Issue
- 1
- Pages
- 24-29
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC443058
- OpenAlex
- W2159417090
- Semantic Scholar
- 8fe2d8db2d3c3ab4a67dd67a612135319f91815b
- Cited by
- 252
- References
- 47
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 9 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 6 · 2013: 4 · 2012: 8
- FWCI
- 12.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Società Italiana dell'Ipertensione Arteriosa
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Keywords
- essential hypertension, hyperinsulinemia, insulin resistance, skeletal muscle, sympathetic nervous system, noradrenaline release, glucose uptake
- MeSH terms
- Adult, Female, Humans, Hypertension, Insulin, Male, Muscles, Norepinephrine, Sympathetic Nervous System
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