GLP‑1 improves palmitate‑induced insulin resistance in human skeletal muscle via SIRT1 activity
Open accessAbstract
The present study investigated whether glucagon like peptide‑1 (GLP‑1) improves glucose uptake through glucose transporter type 4 (GLUT4), mediated by the activation of sirtuin 1 (SIRT1), in skeletal muscle cells with palmitate induced‑insulin resistance. The levels of glucose uptake, GLUT4, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP) were determined in human skeletal muscle myotubes (HSMMs) exposed to palmitate and GLP‑1. Then, to determine whether PKA/cAMP were downstream signals of GLP‑1, a PKA inhibitor was used. To determine whether SIRT‑1 contributes to GLP‑1 action in HSMMs with palmitate‑induced insulin resistance, the levels of peroxisome proliferator‑activated receptor γ coactivator 1α (PGC1α) deacetylation and SIRT‑1 activity were assessed using a SIRT1 inhibitor and small interfering RNA (siRNA). The phosphorylation levels of protein kinase B (Akt) and insulin receptor substrate 1 (IRS‑1) as insulin signaling pathways, were assessed in GLP‑1‑treated HSMMs exposed to palmitate. The influence of SIRT1 on the GLP‑1‑induced activation of insulin signaling pathway was determined using a SIRT1 inhibitor. GLP‑1 restored the palmitate‑induced reductions in the levels of glucose uptake, GLUT4 mRNA, GLUT4 promoter activity, and GLUT4 protein in HSMMs. PKA and cAMP, as GLP‑1 downstream signals, played a role in this process. GLP‑1 increased the deacetylation levels of PGC1α, and stimulated SIRT1 in HSMMs. Moreover, the SIRT1 inhibitor and siRNA of SIRT1 suppressed the effect of GLP‑1 on GLUT4 expression in HSMMs exposed to palmitate. The SIRT1 inhibitor also prevented the GLP‑1‑induced phosphorylation of IRS‑1 and Akt in palmitate‑treated HSMMs. The present findings suggest that in palmitate‑induced insulin‑resistant HSMM, GLP‑1 activates SIRT1 through the PKA/cAMP pathway, which in turn enhances glucose uptake through GLUT4 and the insulin signaling pathway.
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GLP-1 improves PA-induced insulin resistance in human skeletal muscle via SIRT1 activity.
“Jeon et al reported that GLP‑1 improves PA induced insulin resistance in human skeletal muscle via SIRT1 activity.21”
From GLP-1RA Liraglutide and Semaglutide Improves Obesity-Induced Muscle Atrophy via SIRT1 Pathway (2023) · cites this paper as [21]
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- Authors
- Jeon, J., Choi, S., Ha, E., Lee, H., Kim, T., Han, S., Kim, H., Kim, D., Kang, Y., & Lee, K.
- Affiliations
- Ajou University (KR)
- Seoul Medical Center (KR)
- Venue
- International Journal of Molecular Medicine
- Publisher
- Spandidos Publications
- Published
- 2019-07-09
- Volume
- 44
- Issue
- 3
- Pages
- 1161-1171
- ISSN
- 1107-3756 (ISSN-L)
- 1791-244X
- OpenAlex
- W2962539552
- Cited by
- 33
- References
- 53
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 9 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 1
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- AJOU Open Repository (Ajou University) (submittedVersion)
- Funders
- National Research Foundation
- Ajou University
- National Research Foundation of Korea (NRF-2016)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- glucagon-like peptide-1, insulin resistance, palmitate, skeletal muscle, SIRT1, GLUT4, glucose uptake, protein kinase A, cAMP signaling, insulin signaling, Akt, IRS-1
- MeSH terms
- Acetylation, Enzyme Activation, Humans, Insulin Resistance, Models, Biological, Phosphorylation, Recombinant Proteins, Signal Transduction, Muscle, Skeletal, Palmitic Acid, Glucose Transporter Type 4, Glucagon-Like Peptide 1, Sirtuin 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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