CoChat
Sign Up
Cited by 311Diabetes, Cardiovascular Risks, and LipoproteinsCardiovascular and exercise physiologyDiabetes Management and Research

Reflex sympathetic activation induces acute insulin resistance in the human forearm.

Open access
Jamerson, K A, Julius, S, Gudbrandsson, T, Andersson, O, Brant, D O·1993·Hypertension
DOI 10.1161/01.hyp.21.5.618
Open this paper in CoChat — free accountOpen PDF

Abstract

Inferences about the association between sympathetic overactivity and insulin resistance have been drawn from the infusion of sympathomimetic amines in supraphysiological doses. We used the isolated perfused human forearm to investigate the effect of reflex-induced sympathetic nervous system activation on the peripheral utilization of glucose in the skeletal muscles of 14 healthy men. Local hyperinsulinemia in the forearm (132 +/- 25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4 +/- 3.1 mg.dL-1.min-1 per 100 mL forearm volume) to a plateau (85.7 +/- 15.1 mg.dL-1.min-1 per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion but did not alter the utilization of oxygen. Reflex sympathetic nervous system activation was elicited by unloading of cardiopulmonary receptors with bilateral thigh cuff inflation to 40 mm Hg between 60 and 90 minutes of insulin infusion. Blood flow in the forearm was significantly decreased with inflation of thigh cuffs (average decrease of 19%, p < 0.0001). As a result of thigh cuff inflation, there was a reduction in the utilization of glucose (a decrease of 23%, p < 0.02), whereas oxygen utilization was unchanged. We find that an increase in sympathetic nervous system activation (within the normal range of physiological responses) can cause acute insulin resistance in the forearm of healthy volunteers. The reflex caused no change in oxygen utilization, but the same stimulus elicited a decrease in the utilization of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

AI snapshot

Written from the paper’s full text.

TL;DR

In 14 healthy men, reflex sympathetic activation induced by bilateral thigh cuff inflation during local hyperinsulinemia acutely reduced forearm glucose utilization without changing oxygen utilization. The authors conclude that sympathetic activation within the normal physiological range can cause acute insulin resistance in skeletal muscle.

Key findings

  • Local intra-arterial insulin raised forearm plasma insulin from 10.8±1.4 to 132.6±24.7 microunits/mL and increased glucose utilization from 16.4±3.1 to 85.7±15.1 mg·dL⁻¹·min⁻¹ per 100 mL forearm volume, with no change in oxygen utilization.
  • Bilateral thigh cuff inflation to 40 mm Hg decreased forearm blood flow by 19% (p<0.0001) and reduced glucose utilization by 23% (19 mg·dL⁻¹·min⁻¹, p<0.02), whereas oxygen utilization was unchanged.
  • In 11 of 14 subjects, maximal blood flow decrease occurred at 20 minutes, and flow returned to baseline by 30 minutes of cuff inflation; two subjects had no change in forearm blood flow or glucose utilization.
  • The authors conclude that reflex sympathetic activation can cause acute insulin resistance, but the relative contributions of decreased blood flow versus adrenergic receptor-mediated resistance were not resolved.

Methods

  • Isolated perfused human forearm study in 14 healthy men; after a 12-hour fast, intra-arterial insulin was infused for 90 minutes at a rate calculated to raise forearm plasma insulin by 100 microunits/mL over basal levels.
  • Reflex sympathetic activation was elicited by bilateral thigh cuff inflation to 40 mm Hg from 60 to 90 minutes of insulin infusion; forearm blood flow was measured by venous occlusion plethysmography every 10 minutes, with arterial/venous blood gases and plasma glucose/insulin sampled at intervals.
  • Glucose and oxygen balance were expressed as arteriovenous gradients and as the product of gradient and forearm blood flow; changes between conditions were tested with paired t tests.

Limitations

  • The paper states that the study was not primarily designed to assess insulin effects on forearm blood flow, so controls for room temperature, prolonged bed rest, and infusate composition were not addressed.
  • The paper states that it could not resolve the relative importance of vasoconstriction versus β-adrenergic receptor-mediated insulin resistance, and that acute thigh-cuff changes are not a surrogate for chronic hypertension.
  • The paper notes that Fick-principle steady-state after short thigh cuff inflation could be questioned, though the authors argue the 2–4 minute glucose transit time and observed decreased extraction support validity; evident from the text, the final sample was small, all male, and healthy, with no separate control for cuff inflation alone.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1161/01.hyp.21.5.618

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

  • Findingown data
    § Reflex Sympathetic Activation Induces Acute Insulin Resistance in the Human Forearm

    Local hyperinsulinemia in the forearm (132 ±25 microunits/mL for 90 minutes) induced a significant increase in glucose utilization from baseline (16.4±3.1 mg/dL/min per 100 mL forearm volume) to a plateau (85.7±15.1 mg/dL/min per 100 mL forearm volume) between 40 and 60 minutes of insulin infusion.

    “Local hyperinsulinemia in the forearm (132 ±25 microunits/mL for 90 minutes) induced a significant increase in the utilization of glucose from baseline (16.4±3.1 mg • dL”
    Quote in the paperSubstantial claim

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.

  • Recruitment and exclusions leave 15 men, not 14

    Minor

    The stated recruitment and exclusions leave 15 male participants: 18 men minus three men whose studies were terminated. The paper reports results for 14 men without accounting for the additional participant.

  • Baseline arteriovenous glucose gradient differs between results and Table 3

    Minor

    The results give the starting arteriovenous glucose gradient as 4.1±0.6, whereas Table 3 lists the baseline A-V glucose value as 4.5±1.0 mg/dL.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Conway J: A vascular abnormality in hypertension: A study of blood flow in the forearm. Circulation 1963;27:520-529
  2. Hartper RN, Moore MA, Marr MC, Watts LE, Hutchins PM: Arteriolar rarefaction in conjunctiva of human essential hyperten- sives. Microvasc Res 1978;16:369-372

Cited by

Sorted by citations

Related

Authors
Jamerson, K. A., Julius, S., Gudbrandsson, T., Andersson, O., & Brant, D. O.
Affiliations
University of Michigan (US)
ORCID
Jamerson, K A
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1993-05
Volume
21
Issue
5
Pages
618-623
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/01.hyp.21.5.618
OpenAlex
W2002619263
Cited by
311
References
47
Citations by year
2026: 4 · 2025: 10 · 2024: 4 · 2023: 8 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 9 · 2018: 14 · 2017: 6 · 2016: 17 · 2015: 17 · 2014: 16 · 2013: 13 · 2012: 17
FWCI
7.52
Type
journal article
Language
en
Open access
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r37hl037464-10)
  • National Heart, Lung, and Blood Institute (HL-37464, HL-37464-S1, 5 R37 HL-37464, 5 R37 HL-37461-S1)
  • Fogarty International Center (TW04429)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P5606-DK20572)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
reflex sympathetic activation, insulin resistance, hyperinsulinemic-euglycemic clamp, skeletal muscle glucose uptake, cardiopulmonary baroreflex, peripheral blood flow, oxygen utilization, sympathomimetic amines
MeSH terms
Adolescent, Adult, Aged, Constriction, Female, Forearm, Glucose, Hemodynamics, Humans, Injections, Intravenous, Insulin, Insulin Resistance, Male, Middle Aged, Oxygen Consumption, Reflex, Sympathetic Nervous System, Thigh

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review