Cited by 118Regulation of Appetite and ObesityNeuroscience of respiration and sleepHeart Rate Variability and Autonomic Control

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Sympathetic Response to Insulin Is Mediated by Melanocortin 3/4 Receptors in the Hypothalamic Paraventricular Nucleus

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Ward, Kathryn R., Bardgett, James F., Wolfgang, Lawrence, Stocker, Sean D.·2011·Hypertension

DOI 10.1161/hypertensionaha.110.160671PMC PMC3580160

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Abstract

Hyperinsulinemia increases sympathetic nerve activity and contributes to cardiovascular dysfunction in obesity and diabetes. Neurons of the hypothalamic paraventricular nucleus (PVN) regulate sympathetic nerve activity through mono- and poly-synaptic connections to preganglionic neurons in the spinal cord. The purpose of the present study was to determine whether PVN neurons mediate the sympathetic response to insulin. Hyperinsulinemic-euglycemic clamps were performed in α-chloralose-anesthetized, male Sprague-Dawley rats (280–420 g) by an infusion of insulin (3.75 mU/kg per min) and 50% dextrose (0.75–2.0 mL/h) for 120 minutes. At 90 minutes, insulin significantly increased lumbar sympathetic nerve activity without any change in renal sympathetic nerve activity, heart rate, or blood glucose levels. Inhibition of the PVN with bilateral injection of the GABA A receptor agonist muscimol completely reversed the sympathoexcitatory response. However, direct injection of insulin into the PVN did not alter lumbar sympathetic nerve activity, and thereby suggests that insulin activates neurons upstream of the PVN. Interestingly, the sympathetic response to insulin was eliminated by PVN injection of the melanocortin 3/4 receptor antagonist SHU9119, but was unaffected by the angiotensin II type 1 receptor antagonist losartan. A final set of experiments suggests activation of PVN neurons during hyperinsulinemia increases glutamatergic drive to the rostral ventrolateral medulla. Collectively, these findings indicate that insulin activates a melanocortin-dependent pathway to the PVN that increases glutamatergic drive to the rostral ventrolateral medulla and alters cardiovascular function.

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Authors: Ward, K. R., Bardgett, J. F., Wolfgang, L., & Stocker, S. D.
Affiliations: Pennsylvania State University (US)
ORCID: Stocker, Sean D.
Venue: Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2011-03
Volume: 57
Issue: 3
Pages: 435-441
ISSN: 0194-911X (ISSN-L)
1524-4563
DOI: 10.1161/hypertensionaha.110.160671
PMC: PMC3580160
OpenAlex: W2166300547
Cited by: 118
References: 48
Citations by year: 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 12 · 2020: 9 · 2019: 9 · 2018: 1 · 2017: 8 · 2016: 5 · 2015: 11 · 2014: 16 · 2013: 11 · 2012: 13
FWCI: 6.96
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Hypertension (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-090826, R01HL090826)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: insulin, sympathetic activity, melanocortin 3/4 receptor, hypothalamic paraventricular nucleus, hyperinsulinemia, lumbar sympathetic nerve activity, muscimol, SHU9119, losartan, angiotensin II type 1 receptor, rostral ventrolateral medulla, cardiovascular dysfunction, obesity, diabetes mellitus
MeSH terms: Analysis of Variance, Animals, Blood Pressure, Glucose, Heart Rate, Insulin, Male, Medulla Oblongata, Muscimol, Neurons, Paraventricular Hypothalamic Nucleus, Sympathetic Nervous System, Glucose Clamp Technique, Rats, Sprague-Dawley, Losartan, Receptor, Melanocortin, Type 3, Receptor, Melanocortin, Type 4, Rats, Angiotensin Receptor Antagonists, GABA-A Receptor Agonists

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Sympathetic Response to Insulin Is Mediated by Melanocortin 3/4 Receptors in the Hypothalamic Paraventricular Nucleus

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