Evidence map›Paper›PMID 33399911›Full record

ArticleDiabetologia2021

C-C motif chemokine receptor 9 regulates obesity-induced insulin resistance via inflammation of the small intestine in mice.

Takeru Amiya, Nobuhiro Nakamoto, Junichiro Irie, Nobuhito Taniki, Po-Sung Chu, Yuzo Koda, Kentaro Miyamoto, Akihiro Yamaguchi, Shunsuke Shiba, Rei Morikawa and 2 more

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In one paragraph

Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Reversing Dysfunction of CCR9Diabetes, metabolic syndrome and obesity : targets and therapy · 2026
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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

12 authors at 1 institution in 1 country.

Takeru AmiyaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nobuhiro NakamotoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. nobuhiro@z2.keio.jp.ORCID 0000-0001-5203-7444
Junichiro IrieDivision of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Nobuhito TanikiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Po-Sung ChuDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Yuzo KodaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Kentaro MiyamotoDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Akihiro YamaguchiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Shunsuke ShibaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Rei MorikawaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Hiroshi ItohDivision of Endocrinology, Metabolism, and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Takanori KanaiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. takagast@z2.keio.jp.
Keio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisAccumulation of adipose tissue macrophages is considered pivotal in the development of obesity-associated inflammation and insulin resistance. In addition, recent studies suggest an involvement of the intestine as the primary organ in inducing hyperglycaemia and insulin resistance. We have reported that the C-C motif chemokine receptor (CCR) CCR9 is associated with intestinal immunity and has a pathogenic role in various liver diseases. However, its contribution to type 2 diabetes is unknown. In the current study, we aimed to clarify the involvement of CCR9 in the pathology of type 2 diabetes and the potential underlying mechanisms.

methodsTo elucidate how CCR9 affects the development of metabolic phenotypes, we examined the impact of CCR9 deficiency on the pathogenesis of type 2 diabetes using male C57BL/6J (wild-type [WT]) and CCR9-deficient (CCR9 knockout [KO]) mice fed a 60% high-fat diet (HFD) for 12 weeks.

resultsWT and Ccr9KO mice fed an HFD exhibited a comparable weight gain; however, glucose tolerance and insulin resistance were significantly improved in Ccr9KO mice. Moreover, visceral adipose tissue (VAT) and the liver of Ccr9KO mice presented with less inflammation and increased expression of glucose metabolism-related genes than WT mice. Ccr9 and Ccl25 expression were specifically higher in the small intestine but was not altered by HFD feeding and type 2 diabetes development. Accumulation of IFN-γ-producing CD4 CONCLUSIONS/

interpretationCCR9 plays a central role in the pathogenesis of type 2 diabetes by inducing an inflammatory shift in the small intestine. Our findings support CCR9 as a new therapeutic target for type 2 diabetes via the gut-VAT-liver axis.

Indexed as

Insulin ResistanceAnimalsBlood GlucoseCD4-Positive T-LymphocytesCells, CulturedChemokines, CCChemotaxis, LeukocyteDiabetes Mellitus, Type 2Diet, High-FatDisease Models, AnimalEnteritisInflammation MediatorsInsulinInterferon-gammaIntestine, SmallIntra-Abdominal FatBlood GlucoseCC chemokine receptor 9Ccl25 protein, mouseChemokines, CCIFNG protein, mouseInflammation MediatorsInsulinInterferon-gammaReceptors, CCRAdipose tissue macrophageBenign obesityCCR9Chemokine receptorEctopic fat depositionGut permeabilityGut–VAT–liver axisIFN-γ-producing CD4+ T lymphocytesSmall intestinal inflammationType 2 diabetes

Identifiers

PMID33399911
OpenAlexW3120557895

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.