Evidence map›Paper›PMID 39589509›Full record

ArticleDiabetologia2025

Diet-enhanced LRG1 expression promotes insulin hypersecretion and ER stress in pancreatic beta cells.

Desirae D Morales, Jiyoon Ryu, Cong Wei, Jason T Hadley, Maia R Smith, Juli Bai, Juan C Lopez-Alvarenga, Srinivas Mummidi, Ravindranath Duggirala, Jane L Lynch and 2 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. 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
–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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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.

Desirae D MoralesDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0009-0002-7483-0587
Jiyoon RyuDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-7365-0555
Cong WeiDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-4600-8935
Jason T HadleyDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-9631-2185
Maia R SmithDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-8852-1027
Juli BaiDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-1193-8155
Juan C Lopez-AlvarengaDivision of Population Health & Biostatistics, The University of Texas at Rio Grande Valley, Edinburg, TX, USA.ORCID http://orcid.org/0000-0002-0966-8766
Srinivas MummidiDepartment of Health and Behavioral Sciences, Texas A&M University-San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-4068-6380
Ravindranath DuggiralaDepartment of Health and Behavioral Sciences, Texas A&M University-San Antonio, San Antonio, TX, USA.
Jane L LynchDepartment of Pediatrics, The University of Texas Health San Antonio, San Antonio, TX, USA.
Feng LiuNational Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
Lily Q DongDepartment of Cell Systems & Anatomy, The University of Texas Health San Antonio, San Antonio, TX, USA. dongq@uthscsa.edu.

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LUZHE SUN · 1991 to 2026
$59.1M
Cancer Biology Training ProgramT32CA148724 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Pei Wang, Feng-Chun Yang · 2011 to 2026
$3.3M
Adiponectin signaling and macrophage functionR01DK134637 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lily Q Dong, ELIZABETH Ann LEADBETTER · 2023 to 2026
$2.1M
Science as a Team Sport: Leveling the playing field and setting the rules of engagement.T32GM148752 · NIGMS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI GRIFFITH, ANN VENABLES, OYAJOBI, BABATUNDE OLUKAYODE · 2023 to 2024
$874k
Baptist Health Foundation of San Antonio 2020 Strategic to MissionNCI NIH HHS P30 CA054174NCI NIH HHS T32 CA148724NIDDK NIH HHS R01 DK134637NIGMS NIH HHS T32 GM148752NIH HHS R01DK134637
6 · The paper itself

Abstract

aims/hypothesisUpregulation of serum leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in diet-induced obesity and metabolic disorders. However, its specific hormonal actions remain unclear. This study aimed to determine whether diet-enhanced serum LRG1 levels promote hyperinsulinaemia by directly stimulating insulin secretion from pancreatic beta cells.

methodsHuman serum samples were obtained from individuals (both male and female) undergoing plastic surgery. Male C57BL/6 wild-type and Lrg1 whole-body knockout (Lrg1

resultsWe observed a significant positive association between human serum LRG1 levels and both age and BMI, with elevated levels observed in individuals with vs without type 2 diabetes. In mice fed a high-fat diet, LRG1 upregulation in serum was associated with hyperinsulinaemia. Lrg1 knockout protected mice from diet-induced islet hyperplasia and the loss of beta cell mass. Furthermore, neutralising LRG1 activity prevented the onset of diet-induced hyperinsulinaemia and preserved glucose tolerance. Mechanistically, LRG1 induces inositol triphosphate (IP CONCLUSIONS/

interpretationIn summary, this study identifies LRG1 as a significant contributor to hyperinsulinaemia and beta cell dysfunction. Targeting LRG1 activity emerges as a promising therapeutic approach for addressing diet-induced beta cell dysfunction and managing type 2 diabetes.

Indexed as

Endoplasmic Reticulum StressGlycoproteinsInsulinInsulin-Secreting CellsAdultAnimalsDiabetes Mellitus, Type 2Diet, High-FatFemaleHumansHyperinsulinismInsulin SecretionMaleMiceMice, Inbred C57BLMice, KnockoutGlycoproteinsInsulinLRG1 protein, humanLRG1 protein, mouseAdipokineBeta cell failureBeta cellsCa2+ signallingER stressHyperinsulinaemiaInsulin secretionLRG1Type 2 diabetes

Identifiers

PMID39589509
PMCPMC12085111

What Socratic holds

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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.