Evidence mapPaperPMID 39165238Full record

ArticleThe Journal of physiology2025

Intracerebroventricular insulin injection acutely normalizes the augmented exercise pressor reflex in male rats with type 2 diabetes mellitus.

Juan A Estrada, Rie Ishizawa, Han-Kyul Kim, Ayumi Fukazawa, Amane Hori, Norio Hotta, Gary A Iwamoto, Scott A Smith, Wanpen Vongpatanasin, Masaki Mizuno

Abstract read
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Article in The Journal of physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

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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

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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

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Juan A EstradaDepartment of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1252-4840
Rie IshizawaNational Institute of Fitness and Sports, Kanoya University, Kanoya, Japan.
Han-Kyul KimDepartment of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-1048-9543
Ayumi FukazawaDepartment of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-7322-043X
Amane HoriDepartment of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Norio HottaCollege of Life and Health Sciences, Chubu University, Kasugai, Japan.ORCID 0000-0002-3039-5934
Gary A IwamotoDepartment of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Scott A SmithDepartment of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0002-2143-2342
Wanpen VongpatanasinDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Masaki MizunoDepartment of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID 0000-0003-4455-8084

Funding

TARGETING INSULIN RESISTANCE TO IMPROVE ABNORMAL CARDIOVASCULAR CONTROL IN DIABETESR01HL151632 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI MIZUNO, MASAKI · 2020 to 2023
$1.8M
NHLBI NIH HHS R01 HL151632
6 · The paper itself

Abstract

The exercise pressor reflex (EPR) is exaggerated in type 2 diabetes mellitus (T2DM), but the underlying central nervous system aberrations have not been fully delineated. Stimulation of muscle afferents within working skeletal muscle activates the EPR, by sending information to neurons in the brainstem, where it is integrated and results in reflexively increased mean arterial pressure (MAP) and sympathetic nerve activity. Brain insulin is known to regulate neural activity within the brainstem. We hypothesize that brain insulin injection in T2DM rats attenuates the augmented EPR, and that T2DM is associated with decreased brain insulin. Using male Sprague-Dawley rats, T2DM and control rats were generated via an induction protocol with two low doses of streptozotocin (35 and 25 mg/kg, i.p.) in combination with a 14-23-week high-fat diet or saline injections and a low-fat diet, respectively. After decerebration, MAP and renal sympathetic nerve activity (RSNA) were evaluated during EPR stimulation, evoked by electrically induced muscle contraction via ventral root stimulation, before and after (1 and 2 h post) intracerebroventricular (i.c.v.) insulin microinjections (500 mU, 50 nl). i.c.v. insulin decreased peak MAP (ΔMAP Pre (36 ± 14 mmHg) vs. 1 h (21 ± 14 mmHg) vs. 2 h (11 ± 6 mmHg), P < 0.05) and RSNA (ΔRSNA Pre (107.5 ± 40%), vs. 1 h (75.4 ± 46%) vs. 2 h (51 ± 35%), P < 0.05) responses in T2DM, but not controls. In T2DM rats, cerebrospinal fluid insulin was decreased (0.41 ± 0.19 vs. 0.11 ± 0.05 ng/ml, control (n = 14) vs. T2DM (n = 4), P < 0.01). The results demonstrated that insulin injections into the brain normalized the augmented EPR in brain hypoinsulinaemic T2DM rats, indicating that the EPR can be regulated by brain insulin. KEY POINTS: The reflexive increase in blood pressure and sympathetic nerve activity mediated by the autonomic nervous system during muscle contractions is also known as the exercise pressor reflex. The exercise pressor reflex is dangerously augmented in type 2 diabetes, in both rats and humans. In type 2 diabetic rats both cerebrospinal fluid insulin and phosphoinositide 3-kinase signalling within cardiovascular brainstem neurons decrease in parallel. Brain insulin injections decrease the magnitude of the reflexive pressor and sympathetic responses to hindlimb muscle contraction in type 2 diabetic rats. Partial correction of low insulin within the central nervous system in type 2 diabetes may treat aberrant exercise pressor reflex function.

Indexed as

Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2InsulinPhysical Conditioning, AnimalReflexAnimalsBlood PressureInjections, IntraventricularMaleMuscle, SkeletalRatsRats, Sprague-DawleySympathetic Nervous SystemInsulinblood pressureexercise pressor reflexinsulinnucleus tractus solitariusPI3Ksympathetic activity

Identifiers

PMID39165238
PMCPMC12400197

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.