Evidence map›Paper›PMID 42647645›Full record

ArticleScience advances2026

IDE-mediated GLP-1 degradation as the basis for designing long-acting and CNS-stable GLP-1 receptor agonists.

Lu Zhang, Xinyi Liu, Chenfang Si, Xianglong Hou, Xintian Hu, Yelin Chen, Junhao Hu, Christoph W Turck, Bing Shan, Yaoyang Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 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

10 authors.

Lu ZhangInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0009-0001-1942-4538
Xinyi LiuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0009-0008-9328-2372
Chenfang SiInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0000-0002-6604-7464
Xianglong HouInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0000-0002-2992-4691
Xintian HuKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.ORCID 0000-0003-1216-4806
Yelin ChenInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0000-0002-9793-2941
Junhao HuInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0000-0003-0699-1119
Christoph W TurckKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.
Bing ShanInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0000-0003-4178-3526
Yaoyang ZhangInterdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences; 386 Bibo Rd., Shanghai 201210, China.ORCID 0000-0001-5363-9834

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glucagon-like peptide-1 (GLP-1) is a key incretin hormone rapidly degraded by circulating proteases such as DPP-4. The metabolism of GLP-1 by other proteases, particularly tissue-resident proteases, remains largely unexplored. Here, we identify insulin-degrading enzyme (IDE) as a previously unknown GLP-1-degrading protease with two cleavage sites. We show that IDE-mediated degradation of GLP-1, but not insulin, represents a major mechanism regulating glucose control. To resist IDE, we engineered GLP-1 and Semaglutide with D-amino acid substitutions at these sites. These peptides exhibit enhanced stability in plasma, liver and intestinal secretomes, peritoneal fluid, and central nervous system (CNS). D-Ser

Indexed as

Central Nervous SystemGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsInsulysinAnimalsGlucagon-Like Peptide-1 ReceptorGlucagon-Like PeptidesHumansHypoglycemic AgentsMiceProteolysisSemaglutideGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesHypoglycemic AgentsInsulysinSemaglutide

Identifiers

PMID42647645
PMCPMC13510684

What OpenQuestion holds

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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 OpenQuestion graph.