Evidence map›Paper›PMID 41165809›Full record

ArticleCellular and molecular life sciences : CMLS2025

GLP-1 receptor agonist protects glucose-stimulated insulin secretion in pancreatic β-cells against lipotoxicity via PPARδ/UCP2 pathway.

Zhigu Liu, Yalan Chen, Yanna Su, Yueyue Peng, Fen Xu, Bin Yao, Hua Liang, Beisi Lin, Wen Xu

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
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

9 authors.

Zhigu Liu *Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Yalan Chen *Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Yanna SuDepartment of Physical Examination, Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University, Foshan, China.
Yueyue PengDepartment of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Fen XuDepartment of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Bin YaoDepartment of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Hua LiangDepartment of Endocrinology and Metabolism, Shunde Hospital of Southern Medical University, (The First People's Hospital of Shunde), No 1 Penglai Road, Foshan, 528300, Guangdong, China. letitia.yw@163.com.ORCID http://orcid.org/0000-0002-5329-524X
Beisi LinDepartment of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. linbs3@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0001-8542-8265
Wen XuDepartment of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. xwen@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-8258-2707

Funding

Guangzhou Science and Technology Project 202102010175National Natural Science Foundation of China 81770821Natural Science Foundation of Guangdong Province 2022A1515012364
6 · The paper itself

Abstract

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) enhance glucose-stimulated insulin secretion (GSIS). Peroxisome proliferator-activated receptor δ (PPARδ) plays an essential role in mitochondrial function and glucose homeostasis. This study investigated the role of PPARδ in the protective effects of GLP-1RAs on pancreatic β-cells against lipotoxicity. C57BL/6J mice fed a high-fat diet (HFD) for 12 weeks were treated with exenatide (Exe), GW501516 (GW, a PPARδ agonist), saline, or dimethyl sulfoxide (DM) for 8 weeks, followed by phenotypic assessments. In vitro, mouse pancreatic β-cells (NIT-1 cells) were exposed to palmitic acid (PA), PA + exendin-4 (Ex-4), PA + GW, PA + GSK0660 (GSK, a PPARδ antagonist), or PA + Ex-4 + GSK. Compared to HFD mice treated with saline or DM, Exe and GW administration reduced fasting blood glucose, enhanced insulin secretion function and glucose tolerance, and upregulated PPARδ expression. NIT-1 cells treated with PA + Ex-4 and PA + GW showed enhanced GSIS capacity, increased PPARδ expression, decreased UCP2 expression and ADP/ATP ratio, and improved mitochondrial DNA content and mitochondrial membrane potential compared with those treated with PA alone, whereas the opposite results were observed in the PA + GSK group. In the PA + Ex-4 + GSK group, GSK attenuated the effects of Ex-4. PPARδ-knockout (KO) cells treated with PA exhibited similar changes to those treated with PA + GSK, and Ex-4 did not reverse these alterations. Moreover, Ex-4 failed to reverse mitochondrial function or GSIS in pancreatic β-cells with UCP2 overexpression despite an increase in PPARδ expression. Thus, GLP-1RA Exe/Ex-4 preserved GSIS against lipotoxicity in pancreatic β-cells by modulating mitochondrial function through the PPARδ/UCP2 axis.

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsGlucoseInsulinInsulin-Secreting CellsInsulin SecretionPPAR deltaUncoupling Protein 2AnimalsCell LineDiet, High-FatExenatideMaleMiceMice, Inbred C57BLMitochondriaPalmitic AcidExenatideGlucagon-Like Peptide-1 Receptor AgonistsGlucoseGSK0660GW 501516InsulinPalmitic AcidPPAR deltaSulfonesThiazolesThiophenesUcp2 protein, mouseUncoupling Protein 2Glucagon-like peptide 1 receptor agonistsGlucose-stimulated insulin secretionMitochondrial functionPeroxisome proliferator-activated receptor δUncoupling protein 2

Identifiers

PMID41165809
PMCPMC12575910

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.