Evidence mapPaperPMID 41891977Full record

ReviewMolecular medicine reports2026

Succinylation modification in diabetes and diabetic complications: Mechanisms and functions (Review).

Yeteng Xiong, Fei Luo, Bingnan Li, Qinfeng Yang

Abstract readReview
In one paragraph

Review in Molecular medicine reports, 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.

Yeteng XiongThe First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Fei LuoSchool of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Bingnan LiSchool of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Qinfeng YangDivision of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite adequate glycaemic control, diabetic complications frequently progress, underscoring how persistently protein post‑translational modifications (PTMs) contribute to disease pathology by sustaining 'metabolic memory'. Lysine succinylation, a PTM derived from the tricarboxylic acid cycle intermediate succinyl‑CoA and primarily regulated by the desuccinylase sirtuin 5 (SIRT5), has emerged as a key metabolic modulator. By introducing a marked shift in lysine charge, succinylation can notably influence enzyme activity and protein stability. The present review integrates current evidence associating the disruption of the succinyl‑CoA/SIRT5 regulatory axis with impaired metabolic flexibility in diabetes. The mechanisms by which pathological hypersuccinylation compromises mitochondrial bioenergetics, particularly by inhibiting uncoupling protein 1 in obesity and the pyruvate dehydrogenase complex in diabetic cardiomyopathy, are described, and its implications in neurodegeneration within diabetic retinopathy through modification of optineurin are elucidated. The present review also discusses the mechanistic role of epigenetic dysregulation, highlighting how activation of the lysine acetyltransferase 2A/H3K79 succinylation/spermidine/spermine N1‑acetyltransferase family member 2 pathway promotes ferroptosis and inflammation in diabetic kidney disease. The context‑dependent duality of SIRT5 function is also examined; although key in limiting lipotoxicity in cardiomyocytes and podocytes, SIRT5 can paradoxically aggravate glomerular fibrosis in renal mesangial cells by suppressing p53 signalling. The present findings suggested that re‑establishing succinylation homeostasis represents not simply a metabolic correction but a strategic therapeutic objective. However, given the tissue‑specific and frequently opposing effects of SIRT5, future therapeutic approaches should aim to emphasize organ‑targeted delivery rather than systemic modulation to minimize off‑target toxicity while effectively addressing diabetic complications.

Indexed as

Diabetes ComplicationsDiabetes MellitusProtein Processing, Post-TranslationalAcyl Coenzyme AAnimalsDiabetic CardiomyopathiesDiabetic RetinopathyHumansMitochondriaSirtuinsAcyl Coenzyme ASirtuinssuccinyl-coenzyme Adiabetesdiabetic cardiomyopathydiabetic kidney diseasediabetic retinopathyobesitysuccinylation

Identifiers

PMID41891977
PMCPMC13062735

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.