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Effect of Insulin and Glucose Infusions on Sympathetic Nervous System Activity in Normal Man
Abstract
Recent studies indicate a link between carbohydrate intake and the functional state of the sympathetic nervous system. Fasting or carbohydrate restriction decreases sympathetic activity, while glucose ingestion or dietary supplementation with sucrose increases sympathetic nerve activity. To examine the potential contributions of hyperglycemia and hyperinsulinemia to sympathetic stimulation, sympathetic activity was assessed by measurement of plasma norepinephrine (NE) levels and concomitant cardiovascular indices in nonobese young men during glucose and insulin infusions using glucose clamp techniques. In the insulin infusion studies (euglycemic glucose clamp), insulin was administered at 2 mU/kg/min and 5 mU/kg/min for 2 h while blood glucose was maintained at basal levels by a variable rate of glucose infusion. In the hyperglycemic studies, blood glucose was raised 125 mg/dl above basal and maintained at that level for 2h. In response to both insulin infusions, plasma NE rose progressively over the course of the study, increasing 50% with the 2-mU infusion (from mean basal value of 240 ± 34 pg/ml to 360 ± 41 at 150 min, P < 0.001 for changes over time by analysis of variance) and 117% with the 5-mil infusion (from 254 ± 20 pg/ml to 551 ± 88 at 150 min, P < 0.001). The plasma NE response was greater with the 5-mll than with the 2-mU insulin infusion (P < 0.001), and similarly, was greater during the 2-mU insulin infusion than during a control test in which neither insulin nor glucose was infused (P < 0.001). Associated with the elevations in plasma NE In the 2-mU insulin infusion were increases in pulse rate (P < 0.05), pulse pressure (P < 0.005), and pulse rate - systolic blood pressure product (P < 0.01), and during the 5-mU insulin infusions there were increases in pulse pressure (P < 0.001), mean arterial blood pressure (P < 0.001), and pulse rate - systolic blood pressure product (P < 0.001). Plasma NE did not change during the hyperglycemic glucose clamp nor during control tests, and pulse pressure in the hyperglycemic studies (P < 0.005) was the only cardiovascular measurement increased by these two infusion protocols. The clearance of NE in three subjects was unaffected by the 2-mU insulin infusion. Thus, insulin infusion increases sympathetic nervous system activity in the absence of changes in blood glucose.
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“In the present study, infusion of exogenous glucose in amounts comparable to those used in this earlier study (26) also did not increase plasma norepinephrine levels significantly, but evoked highly significant increases in sympathetic discharge targeted at skeletal muscle.”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [26]
In the citing paper
“However, the conclusions of one study were based upon the absence of a detectable effect of glucose infusion on plasma norepinephrine levels (5, 26), a relatively insensitive index of sympathetic discharge (34–36).”
From Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans (1993) · cites this paper as [26]
In the citing paper
“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 [26]
In the citing paper
“Since insulin stimulates the sympathetic nervous system (SNS), 16,17 and since obese patients have increased SNS activity, [18][19][20] a role for insulin-mediated SNS stimulation seems a likely factor in the pathogenesis of high BP in the setting of central obesity.”
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The Effect of Insulin Infusion on Capillary Blood Flow in the Diabetic Neuropathic Foot
Flynn, M. D., Boolell, M., Tooke, J. E., & Watkins, P. (1992) · Diabetic Medicine · doi:10.1111/j.1464-5491.1992.tb01858.x · Cited by 23
Pedersen, O. B. (1989) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610050603 · Cited by 23
Sex-specific effects of an insulin secretagogue in stroke-prone hypertensive rats.
Peuler, J. D., Johnson, B. A., Phare, S. M., et al. (1993) · Hypertension · doi:10.1161/01.hyp.22.2.214 · Cited by 23
Neuropeptide Y prepares rats for scheduled feeding
Drazen, D. L., Wortman, M. D., Seeley, R. J., & Woods, S. C. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00817.2004 · Cited by 23
“In an endocrine sense, the postprandial elevation of plasma fuels has been considered a stressor in that plasma catecholamines, adrenocorticotropic hormone, glucocorticoids, and -endorphin are all elevated at that time (10, 21, 25, 36).”
BackgroundInsulin and Forearm Vasodilation in Hypertension-Prone Men
Hulthén, U. L., Endre, T., Mattiasson, I., & Berglund, G. L. (1995) · Hypertension · doi:10.1161/01.hyp.25.2.214 · Cited by 23
Monnard, C. R., & Grasser, E. K. (2018) · Advances in Nutrition · doi:10.1093/advances/nmx023 · Cited by 23
“Impaired glucose tolerance comprises elevated concentrations of insulin and sympathetic neural activity at rest (51).”
BackgroundCortés‐Ríos, J., & Rodriguez-Fernández, M. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.536146 · Cited by 24
Aging and “Age-Related” Diseases - What Is the Relation?
Kopp, W. (2024) · Aging and Disease · doi:10.14336/ad.2024.0570 · Cited by 31
“Insulin activates the SNS in a dose-dependent manner, as evidenced by increased NE plasma levels and micro-neurographic examinations in insulin infusion studies [190].”
A TELEOLOGICAL VIEW OF OBESITY, DIABETES AND HYPERTENSION
Landsberg, L. (2006) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2006.04455.x · Cited by 22
“Because the energy produced by these reactions occurs in response to cold exposure and dietary intake, two major subcategories are known as non-shivering thermogenesis and dietary thermogenesis.4 Both are regulated by the SNS.”
BackgroundInfluentialSelf-citationAvogaro, A., Valerio, A., Gnudi, L., Maran, A., Miola, M., Duner, E., Marescotti, C., Iori, E., Tiengo, A., & Nosadini, R. (1992) · Diabetologia · doi:10.1007/bf00402544 · Cited by 22
“In this r ega rd , t he re is ev idence tha t excess ively h igh insul in infusion increases the sympa the t i c ne rvous sys t em act ivi ty in the abse nc e of changes in p l a s m a glucose [14].”
BackgroundLu, H., Duanmu, Z., Scislo, T. J., & Dunbar, J. C. (1998) · Clinical and Experimental Hypertension · doi:10.3109/10641969809053213 · Cited by 21
Metadata
- Authors
- Rowe, J. W., Young, J. B., Minaker, K. L., Stevens, A. L., Pallotta, J., & Landsberg, L.
- Affiliations
- Harvard University (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1981-03-01
- Volume
- 30
- Issue
- 3
- Pages
- 219-225
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2111038792
- Cited by
- 1,143
- References
- 0
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 15 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 15 · 2017: 20 · 2016: 19 · 2015: 13 · 2014: 19 · 2013: 15 · 2012: 14
- FWCI
- 23.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- insulin, glucose infusion, sympathetic activity, plasma norepinephrine, hyperinsulinemia, hyperglycemia, hyperinsulinemic-euglycemic clamp, pulse pressure, blood pressure, heart rate, carbohydrate metabolism, young men, dietary sucrose
- MeSH terms
- Adolescent, Adult, Blood Glucose, Blood Pressure, Glucose, Humans, Insulin, Kinetics, Male, Norepinephrine, Pulse, Sympathetic Nervous System
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