Evidence map›Paper›PMID 37147373›Full record

ArticleScientific reports2023

Pancreatic β-cell glutaminase 2 maintains glucose homeostasis under the condition of hyperglycaemia.

Hanna Deguchi-Horiuchi, Sawako Suzuki, Eun Young Lee, Takashi Miki, Noriko Yamanaka, Ichiro Manabe, Tomoaki Tanaka, Koutaro Yokote

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

8 authors at 2 institutions in 1 country.

Hanna Deguchi-HoriuchiDepartment of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Sawako SuzukiDepartment of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, Japan. sawakosuzuki@chiba-u.jp.
Eun Young LeeDepartment of Medical Physiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Takashi MikiDepartment of Medical Physiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Noriko YamanakaDepartment of Disease Biology and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Ichiro ManabeDepartment of Disease Biology and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
Tomoaki TanakaDepartment of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba, Japan.
Koutaro YokoteDepartment of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Chiba University · JPChiba University Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glutaminase 2 (GLS2), a master regulator of glutaminolysis that is induced by p53 and converts glutamine to glutamate, is abundant in the liver but also exists in pancreatic β-cells. However, the roles of GLS2 in islets associated with glucose metabolism are unknown, presenting a critical issue. To investigate the roles of GLS2 in pancreatic β-cells in vivo, we generated β-cell-specific Gls2 conditional knockout mice (Gls2 CKO), examined their glucose homeostasis, and validated the findings using a human islet single-cell analysis database. GLS2 expression markedly increased along with p53 in β-cells from control (RIP-Cre) mice fed a high-fat diet. Furthermore, Gls2 CKO exhibited significant diabetes mellitus with gluconeogenesis and insulin resistance when fed a high-fat diet. Despite marked hyperglycaemia, impaired insulin secretion and paradoxical glucagon elevation were observed in high-fat diet-fed Gls2 CKO mice. GLS2 silencing in the pancreatic β-cell line MIN6 revealed downregulation of insulin secretion and intracellular ATP levels, which were closely related to glucose-stimulated insulin secretion. Additionally, analysis of single-cell RNA-sequencing data from human pancreatic islet cells also revealed that GLS2 expression was elevated in β-cells from diabetic donors compared to nondiabetic donors. Consistent with the results of Gls2 CKO, downregulated GLS2 expression in human pancreatic β-cells from diabetic donors was associated with significantly lower insulin gene expression as well as lower expression of members of the insulin secretion pathway, including ATPase and several molecules that signal to insulin secretory granules, in β-cells but higher glucagon gene expression in α-cells. Although the exact mechanism by which β-cell-specific GLS2 regulates insulin and glucagon requires further study, our data indicate that GLS2 in pancreatic β-cells maintains glucose homeostasis under the condition of hyperglycaemia.

Indexed as

HyperglycemiaInsulin-Secreting CellsIslets of LangerhansAnimalsGlucagonGlucoseGlutaminaseHomeostasisHumansInsulinMiceMice, KnockoutTumor Suppressor Protein p53GlucagonGlucoseGlutaminaseInsulinTumor Suppressor Protein p53

Identifiers

PMID37147373
PMCPMC10162969
OpenAlexW4372332467

What Socratic holds

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LicenceCC BY
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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 Socratic graph.