Evidence map›Paper›PMID 40624143›Full record

ArticleScientific reports2025

Matrix metalloproteinase-2 as a novel regulator of glucose utilization by adipocytes.

Melissa D Lempicki, Ryan J Garrigues, Alexander D Hondros, Tonya N Zeczycki, Brandon L Garcia, John Cavanagh, Thurl E Harris, Akshaya K Meher

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Melissa D LempickiDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA.
Ryan J GarriguesDepartment of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA.
Alexander D HondrosDepartment of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA.
Tonya N ZeczyckiDepartment of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA.
Brandon L GarciaDepartment of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, 66506, USA.
John CavanaghDepartment of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA.
Thurl E HarrisDepartment of Pharmacology, University of Virginia, Charlottesville, VA, 22903, USA.
Akshaya K MeherDepartment of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC, 27858, USA. mehera19@ecu.edu.

Funding

BAFF 60mer as a novel therapeutic target for vascular diseasesR01HL146685 · NHLBI · UNIVERSITY OF VIRGINIA · PI MEHER, AKSHAYA KUMAR · 2019 to 2022
$1.5M
NHLBI NIH HHS R01 HL146685NIH HHS HL146685
6 · The paper itself

Abstract

Glucose transporter 4 (GLUT4) expression on white adipocytes is critical for facilitating cellular uptake of blood glucose, failure of which promotes hyperglycemia. Matrix metalloproteinases (MMPs) play a crucial role in remodeling the white adipose tissue (WAT) during obesity. MMPs have multiple protein substrates, and surprisingly, it is unknown if they can directly target GLUT4 on the adipocyte surface and impair glucose uptake. We identified MMP2 as the highly active gelatinase, a class of MMP, in the gonadal WAT of high-fat diet-induced obese mice. In vitro, metabolic studies in 3T3-L1 adipocytes revealed MMP2 attenuated glucose uptake and glycolysis, which were recovered by an MMP2 inhibitor. In silico structural Analysis using AlphaFold identified a putative MMP2 cleavage site on the extracellular domain of GLUT4. Further, in a substrate competition assay, a peptide mimicking the MMP2 cleavage site on GLUT4 attenuated the cleavage of an MMP substrate by MMP2. Altogether, our results suggest a novel mechanism of impaired glucose utilization by adipocytes, which may contribute to hyperglycemia during obesity.

Indexed as

AdipocytesGlucoseMatrix Metalloproteinase 23T3-L1 CellsAdipose Tissue, WhiteAnimalsDiet, High-FatGlucose Transporter Type 4GlycolysisMaleMiceMice, Inbred C57BLObesityGlucoseGlucose Transporter Type 4Matrix Metalloproteinase 2Slc2a4 protein, mouse

Identifiers

PMID40624143
PMCPMC12234862

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.