Evidence mapPaperPMID 42494871Full record

ReviewFrontiers in endocrinology2026

Ubiquitination modifications as central regulators of metabolic dysfunction in type 2 diabetes mellitus.

Wen-Tao Wang, Ze-Ya Shi, Hai-Long Wang, Zhao-Yang Chen

Abstract readReview
In one paragraph

Review in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

4 authors.

Wen-Tao WangLaboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Jinzhong, China.
Ze-Ya ShiLaboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Jinzhong, China.
Hai-Long WangSchool of Basic Medicine, Shanxi Medical University, Jinzhong, China.
Zhao-Yang ChenLaboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Jinzhong, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance, progressive pancreatic β-cell dysfunction, and multi-organ metabolic dysregulation. Among various post-translational modifications, ubiquitination has emerged as a central regulator of cellular homeostasis, with E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) governing the stability and activity of key signaling proteins. This review systematically elucidates the pivotal role of ubiquitination in the pathogenesis of T2DM. We first outline the fundamental principles of the ubiquitin system, followed by an in-depth discussion of its regulatory mechanisms in insulin-sensitive tissues (liver, skeletal muscle, and adipose tissue) and pancreatic β-cells. We then explore the potential and challenges of targeting specific E3 ligases or DUBs as innovative therapeutic strategies for T2DM. Notably, this review provides three novel perspectives. First, we move from generalized description to enzyme-specific resolution, systematically profiling E3 ligases and DUBs with defined pathological functions in T2DM. Second, we adopt a multi-organ integration approach, highlighting the differential and sometimes heterogeneous roles of the same enzyme across distinct tissues. Third, we shift from a mechanism description a translational orientation, critically evaluating the current status of human evidence, identifying knowledge gaps, and discussing emerging strategies including single-cell omics, spatial transcriptomics, proteomics-based ubiquitination mapping, and artificial intelligence-assisted drug discovery. Collectively, our core conclusion is that E3 ligases and DUBs form tissue-specific regulatory networks governing T2DM pathology. Targeting the ubiquitination system offers new precision therapeutic strategies. Future directions should prioritize integrating multi-omics approaches and AI platforms to accelerate translational applications. This review provides a theoretical foundation for understanding the molecular basis of T2DM and facilitates the development of novel therapeutic interventions.

Indexed as

Diabetes Mellitus, Type 2Protein Processing, Post-TranslationalUbiquitinationAnimalsHumansInsulin ResistanceInsulin-Secreting CellsUbiquitin-Protein LigasesUbiquitin-Protein Ligasesdeubiquitinating enzymeE3 ubiquitin ligaseglycolipid metabolisminsulin resistanceT2DMtherapeutic targetubiquitination

Identifiers

PMID42494871
PMCPMC13391344

What Socratic holds

Textmetadata
LicenceCC BY
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.