Evidence map›Paper›PMID 37314019›Full record

ArticleJournal of diabetes2023

Increased glutamate in type 2 diabetes in the Korean population is associated with increased plasminogen levels.

Hyo Jung Lee, Jeong Won Yeom, Ji Ho Yun, Han Byul Jang, Min-Gyu Yoo, Hyo-Jin Kim, Soo Kyung Koo, Hye-Ja Lee

Abstract read
In one paragraph

Article in Journal of diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
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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

8 authors.

Hyo Jung LeeDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0009-0008-5627-1041
Jeong Won YeomDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0009-0002-2584-0084
Ji Ho YunDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0000-0003-0532-6694
Han Byul JangDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0000-0002-5826-1698
Min-Gyu YooDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0000-0002-8153-6813
Hyo-Jin KimDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0009-0000-6812-6425
Soo Kyung KooDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0000-0002-2133-3088
Hye-Ja LeeDivision of Endocrine and Kidney Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju-si, Chungcheongbuk-do, Korea.ORCID https://orcid.org/0000-0002-7120-1809

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated with type 2 diabetes onset, is induced in the liver.

methodsAn analysis of Korean community-based Ansan-Ansung cohort study data as well as functional research using in vitro and mouse models were performed.

resultsGroups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose-related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK-Hep-1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome-wide association studies. Among glutamate-related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate-induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor-1 (PAI-1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI-1.

conclusionsIncreased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceAnimalsCohort StudiesGenome-Wide Association StudyGlutamic AcidHumansMicePlasminogenPlasminogen Activator Inhibitor 1Republic of KoreaGlutamic AcidPlasminogenPlasminogen Activator Inhibitor 12型糖尿病glutamateKorean Genome and Epidemiology Studymetabotropic glutamate receptor 5plasminogenplasminogen activator inhibitor-1type 2 diabetes代谢性谷氨酸受体5纤溶酶原纤溶酶原激活物抑制剂-1谷氨酸韩国基因组和流行病学研究

Identifiers

PMID37314019
PMCPMC10509517

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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.