Evidence map›Paper›PMID 29590401›Full record

ArticleThe Journal of clinical endocrinology and metabolism2018

Noradrenergic Activity in the Human Brain: A Mechanism Supporting the Defense Against Hypoglycemia.

Renata Belfort-DeAguiar, Jean-Dominique Gallezot, Janice J Hwang, Ahmed Elshafie, Catherine W Yeckel, Owen Chan, Richard E Carson, Yu-Shin Ding, Robert S Sherwin

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 2 pooled it
0.7field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  11. Locus coeruleus-related insula activation supports implicit learning.bioRxiv : the preprint server for biology · 2025
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  20. Integrating brainstem and cortical functional architectures.bioRxiv : the preprint server for biology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Renata Belfort-DeAguiarDepartment of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
Jean-Dominique GallezotPET Center, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut.
Janice J HwangDepartment of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
Ahmed ElshafieDepartment of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
Catherine W YeckelYale School of Public Health, Yale School of Medicine, New Haven, Connecticut.
Owen ChanDepartment of Internal Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Utah, Salt Lake City, Utah.
Richard E CarsonPET Center, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut.
Yu-Shin DingDepartment of Radiology, New York University Medical Center, New York, New York.
Robert S SherwinDepartment of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
Yale University · USNew York University · USUniversity of Utah · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Richard A Flavell · 1993 to 2026
$44.0M
DIABETES MELLITUS &DISORDERS OF METABOLISMT32DK007058 · NIDDK · YALE UNIVERSITY · PI SONIA CAPRIO, Kevan C Herold · 1986 to 2026
$9.6M
GLUCOREGULATORY HORMONE INTERACTIONS IN DIABETESR01DK020495 · NIDDK · YALE UNIVERSITY · PI ROTHMAN, DOUGLAS LYLE · 1986 to 2022
$6.6M
NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK020495NIDDK NIH HHS T32 DK007058
6 · The paper itself

Abstract

Context: Hypoglycemia, one of the major factors limiting optimal glycemic control in insulin-treated patients with diabetes, elicits a brain response to restore normoglycemia by activating counterregulation. Animal data indicate that local release of norepinephrine (NE) in the hypothalamus is important for triggering hypoglycemia-induced counterregulatory (CR) hormonal responses. Objective: To examine the potential role of brain noradrenergic (NA) activation in humans during hypoglycemia. Design: A hyperinsulinemic-hypoglycemic clamp was performed in conjunction with positron emission tomographic imaging. Participants: Nine lean healthy volunteers were studied during the hyperinsulinemic-hypoglycemic clamp. Design: Participants received intravenous injections of (S,S)-[11C]O-methylreboxetine ([11C]MRB), a highly selective NE transporter (NET) ligand, at baseline and during hypoglycemia. Results: Hypoglycemia increased plasma epinephrine, glucagon, cortisol, and growth hormone and decreased [11C]MRB binding potential (BPND) by 24% ± 12% in the raphe nucleus (P < 0.01). In contrast, changes in [11C]MRB BPND in the hypothalamus positively correlated with increments in epinephrine and glucagon levels and negatively correlated with glucose infusion rate (all P < 0.05). Furthermore, in rat hypothalamus studies, hypoglycemia induced NET translocation from the cytosol to the plasma membrane. Conclusions: Insulin-induced hypoglycemia initiated a complex brain NA response in humans. Raphe nuclei, a region involved in regulating autonomic output, motor activity, and hunger, had increased NA activity, whereas the hypothalamus showed a NET-binding pattern that was associated with the individual's CR response magnitude. These findings suggest that NA output most likely is important for modulating brain responses to hypoglycemia in humans.

Indexed as

AdultBlood GlucoseBrainEpinephrineFemaleGlucagonHuman Growth HormoneHumansHydrocortisoneHypoglycemiaMaleNorepinephrinePositron-Emission TomographyBlood GlucoseEpinephrineGlucagonHuman Growth HormoneHydrocortisoneNorepinephrine

Identifiers

PMID29590401
PMCPMC6456998
OpenAlexW2793327253

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.