Evidence map›Paper›PMID 33895325›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021

The phosphatidylserine flippase β-subunit Tmem30a is essential for normal insulin maturation and secretion.

Yeming Yang, Kuanxiang Sun, Wenjing Liu, Xiao Li, Wanli Tian, Ping Shuai, Xianjun Zhu

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

18 citing papers in PubMed, 27 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

7 authors at 1 institution in 1 country.

Yeming YangHealth Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Kuanxiang SunThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Wenjing LiuThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Xiao LiThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Wanli TianThe Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
Ping ShuaiHealth Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072 China. Electronic address: shuaiping@med.uestc.edu.cn.
Xianjun ZhuHealth Management Center, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Center for Medical Genetics, Prenatal Diagnosis Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China; Key Laboratory of Tibetan Medicine Research, Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Xining, Qinghai 810008, China; Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026), Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072 China; Natural Products Research Center, Institute of Chengdu Biology, Sichuan Translational Medicine Hospital, Chinese Academy of Sciences, Chengdu, Sichuan 610072, China; Department of Ophthalmology, First People's Hospital of Shangqiu, Shangqiu, Hennan 476100, China. Electronic address: xjzhu@uestc.edu.cn.
University of Electronic Science and Technology of China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The processing, maturation, and secretion of insulin are under precise regulation, and dysregulation causes profound defects in glucose handling, leading to diabetes. Tmem30a is the β subunit of the phosphatidylserine (PS) flippase, which maintains the membrane asymmetric distribution of PS. Tmem30a regulates cell survival and the localization of subcellular structures and is thus critical to the normal function of multiple physiological systems. Here, we show that conditional knockout of Tmem30a specifically in pancreatic islet β cells leads to obesity, hyperglycemia, glucose intolerance, hyperinsulinemia, and insulin resistance in mice, due to insufficient insulin release. Moreover, we reveal that Tmem30a plays an essential role in clathrin-mediated vesicle transport between the trans Golgi network (TGN) and the plasma membrane (PM), which comprises immature secretory granule (ISG) budding at the TGN. We also find that Tmem30a deficiency impairs clathrin-mediated vesicle budding and thus blocks both insulin maturation in ISGs and the transport of glucose-sensing Glut2 to the PM. Collectively, these disruptions compromise both insulin secretion and glucose sensitivity, thus contributing to impairments in glucose-stimulated insulin secretion. Taken together, our data demonstrate an important role of Tmem30a in insulin maturation and glucose metabolic homeostasis and suggest the importance of membrane phospholipid distribution in metabolic disorders.

Indexed as

AnimalsCell MembraneDisease Models, AnimalGene Knockout TechniquesGlucoseGlucose IntoleranceGlucose Transporter Type 2HyperglycemiaHyperinsulinismInsulinInsulin ResistanceInsulin-Secreting CellsInsulin SecretionMembrane ProteinsMiceObesityGlucoseGlucose Transporter Type 2InsulinMembrane ProteinsPhosphatidylserinesSlc2a2 protein, mouseTMEM30a protein, mouseglucose intolerancehyperglycemiaInsulin secretionphosphatidylserine flippaseTmem30aType 2 diabetes mellitus

Identifiers

PMID33895325
PMCPMC8417432
OpenAlexW3157056301

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.