Evidence map›Paper›PMID 40754229›Full record

ArticleMolecular metabolism2025

Inhibition of Unc119b improves insulin sensitivity through potentiation of Rac1 activation in skeletal muscle and brown adipose tissue.

Ayushi Mittal, Paul Buscaglia, Dhiraj Srivastava, Nikolai O Artemyev, Julien A Sebag

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 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. 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

5 authors.

Ayushi MittalDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Elizabeth Weiser Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa city, 52242, USA.
Paul BuscagliaDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Elizabeth Weiser Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Dhiraj SrivastavaDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa city, 52242, USA.
Nikolai O ArtemyevDepartment of Molecular Physiology and Biophysics, University of Iowa, Iowa city, 52242, USA.
Julien A SebagDepartment of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA; Elizabeth Weiser Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI, 48109, USA; Life Science institute, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: jsebag@med.umich.edu.

Funding

REGULATION OF ROD CYCLIC GMP PHOSPHODIESTERASER01EY010843 · NEI · UNIVERSITY OF IOWA · PI Nikolai O Artemyev · 1995 to 2026
$8.9M
MOLECULAR MECHANISM OF PHOTORECEPTOR G PROTEIN SIGNALINGR01EY012682 · NEI · UNIVERSITY OF IOWA · PI ARTEMYEV, NIKOLAI O · 2000 to 2022
$7.5M
Role and mechanism of Unc119b in the regulation of glucose homeostasisR01DK138932 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Julien Albert Sebag · 2025 to 2026
$1.1M
NEI NIH HHS R01 EY010843NEI NIH HHS R01 EY012682NIDDK NIH HHS R01 DK138932
6 · The paper itself

Abstract

objectivesA hallmark of type II diabetes is an impairment of the glucose transporter GLUT4 translocation to the plasma membrane of specialized cells in response to insulin. Identifying mechanisms involved in this defect is critical to developing treatments that restore insulin sensitivity. We previously identified a small molecule insulin sensitizer, C59, which improves insulin-stimulated GLUT4 translocation through binding to Unc119b, however, the role and mechanism of Unc119b-mediated regulation of GLUT4 trafficking is unknown.

methodsHere we use in vitro systems and rodent models of insulin resistance with genetic manipulations of Unc119b expression to uncover the role of this protein in the regulation of glucose homeostasis.

resultsWe demonstrate that Unc119b is an endogenous inhibitor of GLUT4 translocation which contributes to the development of insulin resistance in obese individuals. We show that Unc119b interacts with Rac1 and inhibits its activation by insulin, resulting in reduced GLUT4 translocation. Both the prenylated C-terminus of Rac1 and C59 bind to the same site within Unc119b, thus suggesting that C59 enhances GLUT4 translocation by interfering with the action of Unc119b on Rac1.

conclusionsOverall, this study identifies Unc119b as a critical regulator of glucose homeostasis, uncovers its role in GLUT4 trafficking, and identifies the mechanism of action of a new class of insulin sensitizers.

Indexed as

Adaptor Proteins, Signal TransducingInsulin ResistanceMuscle, Skeletalrac1 GTP-Binding ProteinAnimalsDiabetes Mellitus, Type 2GlucoseGlucose Transporter Type 4HumansInsulinMaleMiceMice, Inbred C57BLObesityProtein TransportRatsAdaptor Proteins, Signal TransducingGlucoseGlucose Transporter Type 4Insulinrac1 GTP-Binding ProteinDiabetesGlucose toleranceGLUT4 translocationInsulin sensitivityRac1Unc119b

Identifiers

PMID40754229
PMCPMC12791835

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.