Effect of liraglutide on expression of inflammatory genes in type 2 diabetes
Abstract Anti-inflammatory effects of glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment in T2D may contribute to the cardiovascular benefits observed with GLP-1 RAs in outcome studies. We investigated if the GLP-1 RA liraglutide exerts anti-inflammatory effects through modulation of infl...
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2021
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oai:doaj.org-article:44a015485b9644c7a5d5d44744afea422021-12-02T17:23:39ZEffect of liraglutide on expression of inflammatory genes in type 2 diabetes10.1038/s41598-021-97967-02045-2322https://doaj.org/article/44a015485b9644c7a5d5d44744afea422021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97967-0https://doaj.org/toc/2045-2322Abstract Anti-inflammatory effects of glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment in T2D may contribute to the cardiovascular benefits observed with GLP-1 RAs in outcome studies. We investigated if the GLP-1 RA liraglutide exerts anti-inflammatory effects through modulation of inflammatory gene expression in peripheral blood mononuclear cells (PBMCs). From 54 participants of a double-blinded trial where individuals with type 2 diabetes (T2D) were randomized to liraglutide (1.8 mg/day) or placebo for 26 weeks, a sub-study was performed in which PBMCs were extracted from fresh blood at study start and at end-of-treatment. The expression of selected inflammatory genes in PBMCs were measured by quantitative real-time polymerase chain reaction (PCR). Moreover, the expression of the GLP-1 receptor (GLP1R) was examined in a subset (n = 40) of the PBMC samples. The human monocytic cell line THP-1 was used for in vitro GLP-1 exposure experiments. The expression of tumor necrosis factor-α (TNFA) (p = 0.004) and interleukin-1β (IL1B) was downregulated (p = 0.046) in the liraglutide-treated group (n = 31), and unchanged in the placebo group (n = 21, p ≥ 0.11), with no significant differences between the two groups (p ≥ 0.67). The expression of interferon-γ (IFNG) and cluster of differentiation 163 (CD163) were upregulated in both groups (p ≤ 0.006) with no differences between groups (p ≥ 0.47). C–C Motif Chemokine Ligand 5 (CCL5) was upregulated in the liraglutide-treated group (p = 0.002) and unchanged in the placebo group (p = 0.14), with no significant difference between groups (p = 0.36). Intercellular adhesion molecule 1 (ICAM1) was unchanged in both groups (p ≥ 0.43). GLP1R expression in the PBMCs was undetectable. In vitro experiments showed no effect of GLP-1 treatment on inflammatory gene expression in THP-1 cells. GLP1R expression in THP-1 cells was not detectable. In summary, we observed a discrete modulatory effect of liraglutide on the expression of inflammatory genes in PBMCs. The lack of evidence for GLP1R expression in PBMCs and THP-1 cells suggests that possible effects of liraglutide on the PBMCs’ gene expression are most likely indirect. Further investigations are needed to establish the anti-inflammatory potential of GLP-1 RAs.Emilie H. ZobelRasmus S. RipaBernt J. von ScholtenViktor Rotbain CurovicAndreas KjaerTine W. HansenPeter RossingJoachim StørlingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021) |
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Medicine R Science Q Emilie H. Zobel Rasmus S. Ripa Bernt J. von Scholten Viktor Rotbain Curovic Andreas Kjaer Tine W. Hansen Peter Rossing Joachim Størling Effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| description |
Abstract Anti-inflammatory effects of glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment in T2D may contribute to the cardiovascular benefits observed with GLP-1 RAs in outcome studies. We investigated if the GLP-1 RA liraglutide exerts anti-inflammatory effects through modulation of inflammatory gene expression in peripheral blood mononuclear cells (PBMCs). From 54 participants of a double-blinded trial where individuals with type 2 diabetes (T2D) were randomized to liraglutide (1.8 mg/day) or placebo for 26 weeks, a sub-study was performed in which PBMCs were extracted from fresh blood at study start and at end-of-treatment. The expression of selected inflammatory genes in PBMCs were measured by quantitative real-time polymerase chain reaction (PCR). Moreover, the expression of the GLP-1 receptor (GLP1R) was examined in a subset (n = 40) of the PBMC samples. The human monocytic cell line THP-1 was used for in vitro GLP-1 exposure experiments. The expression of tumor necrosis factor-α (TNFA) (p = 0.004) and interleukin-1β (IL1B) was downregulated (p = 0.046) in the liraglutide-treated group (n = 31), and unchanged in the placebo group (n = 21, p ≥ 0.11), with no significant differences between the two groups (p ≥ 0.67). The expression of interferon-γ (IFNG) and cluster of differentiation 163 (CD163) were upregulated in both groups (p ≤ 0.006) with no differences between groups (p ≥ 0.47). C–C Motif Chemokine Ligand 5 (CCL5) was upregulated in the liraglutide-treated group (p = 0.002) and unchanged in the placebo group (p = 0.14), with no significant difference between groups (p = 0.36). Intercellular adhesion molecule 1 (ICAM1) was unchanged in both groups (p ≥ 0.43). GLP1R expression in the PBMCs was undetectable. In vitro experiments showed no effect of GLP-1 treatment on inflammatory gene expression in THP-1 cells. GLP1R expression in THP-1 cells was not detectable. In summary, we observed a discrete modulatory effect of liraglutide on the expression of inflammatory genes in PBMCs. The lack of evidence for GLP1R expression in PBMCs and THP-1 cells suggests that possible effects of liraglutide on the PBMCs’ gene expression are most likely indirect. Further investigations are needed to establish the anti-inflammatory potential of GLP-1 RAs. |
| format |
article |
| author |
Emilie H. Zobel Rasmus S. Ripa Bernt J. von Scholten Viktor Rotbain Curovic Andreas Kjaer Tine W. Hansen Peter Rossing Joachim Størling |
| author_facet |
Emilie H. Zobel Rasmus S. Ripa Bernt J. von Scholten Viktor Rotbain Curovic Andreas Kjaer Tine W. Hansen Peter Rossing Joachim Størling |
| author_sort |
Emilie H. Zobel |
| title |
Effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| title_short |
Effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| title_full |
Effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| title_fullStr |
Effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| title_full_unstemmed |
Effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| title_sort |
effect of liraglutide on expression of inflammatory genes in type 2 diabetes |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/44a015485b9644c7a5d5d44744afea42 |
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