Evidence map›Paper›PMID 26336514›Full record

ArticleDiabetology & metabolic syndrome2015

Pioglitazone alters monocyte populations and stimulates recent thymic emigrants in the BBDZR/Wor type 2 diabetes rat model.

Bradley T Gao, Ryan P Lee, Youde Jiang, Jena J Steinle, Vanessa M Morales-Tirado

Open access · goldAbstract read
In one paragraph

Article in Diabetology & metabolic syndrome, 2015. 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
0.4field-weighted citation impact, top 38% 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, 11 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

Bradley T GaoDepartment of Ophthalmology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA.
Ryan P LeeDepartment of Ophthalmology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA.
Youde JiangDepartment of Ophthalmology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA.
Jena J SteinleDepartment of Ophthalmology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA ; Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA ; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI USA.
Vanessa M Morales-TiradoDepartment of Ophthalmology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA ; Department of Microbiology, Immunology and Biochemistry, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 USA.
University of Tennessee Health Science Center · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
$24.3M
Vision Research CoreP30EY021721 · NEI · UNIVERSITY OF FLORIDA · PI HAUSWIRTH, WILLIAM W · 2011 to 2015
$2.8M
Mechanisms of TNFalpha-Induced Insulin Resistance in Retinal CellsR01EY022330 · NEI · WAYNE STATE UNIVERSITY · PI STEINLE, JENA J · 2013 to 2017
$1.5M
NEI NIH HHS P30 EY021721NEI NIH HHS R01 EY022330NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

backgroundType 2 diabetes is commonly characterized by insulin deficiency and decreased sensitivity of insulin receptors, leading to a chronic state of hyperglycemia in individuals. Disease progression induces changes in the immune profile that engenders a chronic inflammatory condition. Thiazolidinedione (TDZ) drugs, such as Pioglitazone (Pio), aid in controlling disease symptoms. While the mechanisms by which Pio controls hyperglycemia are beginning to be understood, relatively little is known about the effects of Pio on suppression of the systemic immune phenotype, attributed to visceral adipose tissue and macrophages.

methodsHere, we utilize the recently developed BBDZR/Wor type 2 diabetes rat model to test our hypothesis that a selective in vivo growth of CD3(+)T cells in the spleen contributes to the increase in T lymphocytes, including Tregs, independent of visceral adipose tissue. We investigated the systemic effects of Pio on multifactorial aspects of the disease-induced immune phenotype both in vivo and in vitro in normal, non-diabetic animals and in disease.

resultsOur work revealed that Pio reversed the lymphopenic status of diabetic rats, in part by an increase in CD3(+) T lymphocytes and related subsets. Moreover, we found evidence that Pio caused a selective growth of newly differentiated T lymphocytes, based on the presence of recent thymic emigrants in vivo. To investigate effects of Pio on the inflammatory milieu, we examined the production of the signature cytokines TNF-α and IL-1β and found they were reduced by Pio-treatment, while the levels of IL-4, an anti-inflammatory mediator, were significantly increased in a Pio-dependent manner. The increase in IL-4 production, although historically attributed to macrophages from visceral adipose tissue under other conditions, came also from CD3(+) T lymphocytes from the spleen, suggesting splenocytes contribute to the Pio-induced shift towards an anti-inflammatory phenotype.

conclusionsWe show for the first time that Pio treatment significantly suppresses the systemic inflammatory status in the BBDZR/Wor type 2 diabetes rat model by the selective growth of newly differentiated CD3(+) T cells and by increasing CD3(+)IL-4 production in immigrant spleen lymphocytes.

Indexed as

ImmunomodulationPioglitazoneRecent thymic emigrantsType 2 diabetes

Identifiers

PMID26336514
PMCPMC4557231
OpenAlexW1745474107

What OpenQuestion 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 OpenQuestion graph.