Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.
Open accessAbstract
Hyperinsulinemia may contribute to hypertension by increasing sympathetic activity and vascular resistance. We sought to determine if insulin increases central sympathetic neural outflow and vascular resistance in humans. We recorded muscle sympathetic nerve activity (MSNA; microneurography, peroneal nerve), forearm blood flow (plethysmography), heart rate, and blood pressure in 14 normotensive males during 1-h infusions of low (38 mU/m2/min) and high (76 mU/m2/min) doses of insulin while holding blood glucose constant. Plasma insulin rose from 8 +/- 1 microU/ml during control, to 72 +/- 8 and 144 +/- 13 microU/ml during the low and high insulin doses, respectively, and fell to 15 +/- 6 microU/ml 1 h after insulin infusion was stopped. MSNA, which averaged 21.5 +/- 1.5 bursts/min in control, increased significantly (P less than 0.001) during both the low and high doses of insulin (+/- 5.4 and +/- 9.3 bursts/min, respectively) and further increased during 1-h recovery (+15.2 bursts/min). Plasma norepinephrine levels (119 +/- 19 pg/ml during control) rose during both low (258 +/- 25; P less than 0.02) and high (285 +/- 95; P less than 0.01) doses of insulin and recovery (316 +/- 23; P less than 0.01). Plasma epinephrine levels did not change during insulin infusion. Despite the increased MSNA and plasma norepinephrine, there were significant (P less than 0.001) increases in forearm blood flow and decreases in forearm vascular resistance during both doses of insulin. Systolic pressure did not change significantly during infusion of insulin and diastolic pressure fell approximately 4-5 mmHg (P less than 0.01). This study suggests that acute increases in plasma insulin within the physiological range elevate sympathetic neural outflow but produce forearm vasodilation and do not elevate arterial pressure in normal humans.
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In lean subjects, sympathetic activation evoked by acute elevation of plasma insulin to high physiological concentrations does not raise blood pressure.
“In lean subjects, sympathetic activation evoked by acute elevation of plasma insulin to high physiological concentrations does not raise blood pressure (12–14)”
From Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. (1994) · cites this paper as [12]
The Abstract and Conclusion (pages not provided) report that acute insulin infusion increased sympathetic nerve activity without increasing arterial pressure in normal humans. The Subjects section describes 14 healthy males with BMIs ranging from 21 to 32; it does not establish the result specifically for lean subjects. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn lean healthy subjects, insulin-induced stimulation of muscle blood flow is consistently accompanied by a marked stimulation of sympathetic neural outflow to the same vascular bed.
“In lean healthy subjects, insulin-induced stimulation of muscle blood flow consistently is accompanied by a marked stimulation of sympathetic neural outflow to the same vascular bed (12-14).”
From Impaired insulin-induced sympathetic neural activation and vasodilation in skeletal muscle in obese humans. (1994) · cites this paper as [12]
The Discussion reports that insulin increased muscle sympathetic nerve activity while causing forearm vasodilation in healthy subjects. But it explicitly says blood flow was measured in the forearm and nerve activity in the leg, so the study does not establish both effects in the same vascular bed. The Subjects section also reports BMI values up to 32, rather than an exclusively lean group. (LLM, conf=0.90)
Experimental — accuracy not yet measuredA balance between insulin's opposing sympathoexcitatory pressor and vasodilatory depressor effects may explain that in lean healthy subjects acute hyperinsulinemia at high physiologic concentrations does not raise arterial pressure.
“Second, a balance between insulin's opposing sympathoexcitatory pressor and vasodilatory depressor effects may offer a potential explanation for the present, and earlier (6, 7, 26) observations, that in lean healthy subjects acute hyperinsulinemia at high physiologic concentrations does not raise arterial pressure.”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [6]
The Discussion says that sympathetic pressor and vasodilatory depressor actions appear relatively balanced during acute insulin increases in the physiologic postprandial range, so arterial pressure does not rise. The Subjects section describes healthy males, but their BMI ranged from 21 to 32; the paper does not establish the finding specifically for lean subjects. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAn earlier study found a small but significant decrease in diastolic blood pressure during insulin/glucose infusion in humans.
“In this regard, an earlier study found a small but significant decrease in diastolic blood pressure during insulin/glucose infusion in humans (6).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [6]
In humans, acute euglycemic hyperinsulinemia stimulates both sympathetic efferent activity and blood flow in skeletal muscle.
“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 [6]
Heart rate cannot be taken as either a marker of cardiac sympathetic adrenergic activity or a reliable indicator of sympathetic activity to other regional circulations.
“These and other studies24,25 indicate that despite the ease of measurement, heart rate cannot be taken as either a marker of cardiac sympathetic adrenergic activity or a reliable indicator of sympathetic activity to other regional circulations.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [25]
Despite insulin-induced sympathetic activation, insulin failed to increase blood pressure because the sympathetic vasoconstriction was opposed and overridden by a vasodilator action of insulin.
“The surprising finding was that despite insulin-induced sympathetic activation, insulin failed to increase blood pressure because the sympathetic vasoconstriction was opposed and overridden by a vasodilator action of insulin25.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [25]
Insulin vasodilates skeletal muscle and coronary vasculature.
“Insulin vasodilates skeletal muscle6, 37 and coronary38, 39 vasculature.”
From The Vasculature in Prediabetes (2018) · cites this paper as [37]
Studies with the euglycaemic clamp have yielded conflicting results in humans regarding blood flow: some reported increased blood flow in skeletal muscles of the limbs, whereas others reported unchanged blood flow.
“Studies with the euglycaemic clamp have yielded conflicting results in humans.A number of studies have reported an increased blood flow in skeletal muscles of the limbs [14,26,[34][35][36], whereas others have reported unchanged blood flow [37][38][39].”
From The sympathetic response to euglycaemic hyperinsulinaemia: Evidence from microelectrode nerve recordings in healthy subjects (1992) · cites this paper as [14]
Neither the present study nor Anderson et al. displayed any convincing evidence for a rise in blood pressure during experimental hyperinsulinaemia.
“Neither the present study nor that by Anderson et al. [14] displayed any convincing evidence for a rise in blood pressure during experimental hyperinsulinaemia.”
From The sympathetic response to euglycaemic hyperinsulinaemia: Evidence from microelectrode nerve recordings in healthy subjects (1992) · cites this paper as [14]
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References 37 · Cited by 1,075
Research works printed but not linked: 1
- Landsberg, L., and J. B. Young. 1985. The influence ofdiet on the sympa- thetic nervous system. In Neuroendocrine Perspectives. E. E. Muller, R. M. MacLeod, and L. A. Frohman, editors. Elsevier Science Publishers. 191-218.
- Authors
- Anderson, E. A., Hoffman, R. P., Balon, T. W., Sinkey, C. A., & Mark, A. L.
- Affiliations
- University of Iowa (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1991-06-01
- Volume
- 87
- Issue
- 6
- Pages
- 2246-2252
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296986
- OpenAlex
- W1966150597
- Cited by
- 1,075
- References
- 37
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 19 · 2023: 18 · 2022: 17 · 2021: 20 · 2020: 14 · 2019: 14 · 2018: 16 · 2017: 20 · 2016: 26 · 2015: 27 · 2014: 26 · 2013: 33 · 2012: 34
- FWCI
- 33.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50hl044546-05, 5r29hl043514-05)
- National Heart, Lung, and Blood Institute (HL-24962, HL-43514, HL-44546)
- 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 › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- hyperinsulinemia, sympathetic activity, muscle sympathetic nerve activity, vasodilation, forearm blood flow, vascular resistance, norepinephrine, epinephrine, blood pressure, hypertension, insulin infusion, normotensive subjects
- MeSH terms
- Adult, Arm, Blood Glucose, Blood Pressure, Catecholamines, Heart Rate, Humans, Hyperinsulinism, Male, Muscles, Potassium, Regional Blood Flow, Sympathetic Nervous System, Vascular Resistance, Vasodilation
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