Evidence map›Paper›PMID 33148883›Full record

ArticleJCI insight2020

Repeated hypoglycemia remodels neural inputs and disrupts mitochondrial function to blunt glucose-inhibited GHRH neuron responsiveness.

Mitchell Bayne, Alexandra Alvarsson, Kavya Devarakonda, Rosemary Li, Maria Jimenez-Gonzalez, Darline Garibay, Kaetlyn Conner, Merina Varghese, Madhavika N Serasinghe, Jerry E Chipuk and 2 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. GHRH in diabetes and metabolism.Reviews in endocrine & metabolic disorders · 2025
    Review
  3. Review
  4. Review
  5. Article
  6. Acute severe hypoglycemia alters mouse brain microvascular proteome.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  7. Review
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

12 authors at 3 institutions in 2 countries.

Mitchell BayneDiabetes, Obesity and Metabolism Institute.
Alexandra AlvarssonDiabetes, Obesity and Metabolism Institute.
Kavya DevarakondaDiabetes, Obesity and Metabolism Institute.
Rosemary LiDiabetes, Obesity and Metabolism Institute.
Maria Jimenez-GonzalezDiabetes, Obesity and Metabolism Institute.
Darline GaribayDiabetes, Obesity and Metabolism Institute.
Kaetlyn ConnerDiabetes, Obesity and Metabolism Institute.
Merina VargheseNash Family Department of Neuroscience and Friedman Brain Institute, and.
Madhavika N SerasingheTisch Cancer Institute and Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jerry E ChipukTisch Cancer Institute and Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Patrick R HofNash Family Department of Neuroscience and Friedman Brain Institute, and.
Sarah A StanleyDiabetes, Obesity and Metabolism Institute.
Institute of Nutrition, Metabolism and Diabetes · CAAllen Institute for Brain Science · USTisch Hospital · US

Funding

Translational Research CoreP30DK020541 · NIDDK · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI STREAMSON C CHUA · 2015 to 2026
$27.7M
Training Program in NeuroscienceT32MH087004 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GEORGE W. HUNTLEY · 2009 to 2026
$4.0M
Remote Electromagnetic Control of Neural Activity for Treatment of Parkinson's DiseaseR01NS097184 · NINDS · ROCKEFELLER UNIVERSITY · PI DORDICK, JONATHAN S., FRIEDMAN, JEFFREY M · 2016 to 2020
$3.4M
Function and Regulation of the BCL-2 FamilyR01CA237264 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHIPUK, JERRY EDWARD · 2020 to 2024
$1.9M
(PQ5) Role of Mitochondrial Division in Cancer BiologyR01CA206005 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHIPUK, JERRY EDWARD · 2016 to 2020
$1.7M
Remote regulation of neural activityU01MH105941 · NIMH · ROCKEFELLER UNIVERSITY · PI STANLEY, SARAH AMY · 2014 to 2016
$1.2M
Remote Modulation of the Peripheral Nervous SystemOT2OD024912 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI STANLEY, SARAH AMY · 2017 to 2019
$1.1M
NCI NIH HHS R01 CA206005NCI NIH HHS R01 CA237264NIDDK NIH HHS P30 DK020541NIH HHS OT2 OD024912NIMH NIH HHS T32 MH087004NIMH NIH HHS U01 MH105941NINDS NIH HHS R01 NS097184
6 · The paper itself

Abstract

Hypoglycemia is a frequent complication of diabetes, limiting therapy and increasing morbidity and mortality. With recurrent hypoglycemia, the counterregulatory response (CRR) to decreased blood glucose is blunted, resulting in hypoglycemia-associated autonomic failure (HAAF). The mechanisms leading to these blunted effects are only poorly understood. Here, we report, with ISH, IHC, and the tissue-clearing capability of iDISCO+, that growth hormone releasing hormone (GHRH) neurons represent a unique population of arcuate nucleus neurons activated by glucose deprivation in vivo. Repeated glucose deprivation reduces GHRH neuron activation and remodels excitatory and inhibitory inputs to GHRH neurons. We show that low glucose sensing is coupled to GHRH neuron depolarization, decreased ATP production, and mitochondrial fusion. Repeated hypoglycemia attenuates these responses during low glucose. By maintaining mitochondrial length with the small molecule mitochondrial division inhibitor-1, we preserved hypoglycemia sensitivity in vitro and in vivo. Our findings present possible mechanisms for the blunting of the CRR, significantly broaden our understanding of the structure of GHRH neurons, and reveal that mitochondrial dynamics play an important role in HAAF. We conclude that interventions targeting mitochondrial fission in GHRH neurons may offer a new pathway to prevent HAAF in patients with diabetes.

Indexed as

AnimalsAutonomic Nervous SystemFemaleGlucoseGrowth Hormone-Releasing HormoneHypoglycemiaMaleMiceMice, Inbred C57BLMitochondriaNeuronsPure Autonomic FailureSweetening AgentsGlucoseGrowth Hormone-Releasing HormoneSweetening AgentsDiabetesMetabolismNeuroscience

Identifiers

PMID33148883
PMCPMC7710320
OpenAlexW3097602241

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.