<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Introduction</bold>. Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers.L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM).<bold>Materials and Methods</bold>. 15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method.<bold>Results</bold>. In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased <italic>SIRT1</italic> expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level.<bold>Conclusions</bold>. L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.</abstract>

Introduction. Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of inflammatory biomarkers.L can influence NF-kB inflammatory cascade, but the mechanisms of anti-inflammatory activities of L remain to be determined. In animal models L influenced an activity of Sirtuin 1(SIRT1). Moreover, recent evidences strongly suggest that SIRT1 up-regulation may serve as a potent therapeutic approach against development and progression of diabetic complications. The aim of this study was to investigate L effects directed on the pro-inflammatory NF-kB pathway and expression of SIRT1 in obese patients with type 2 diabetes mellitus (DM).Materials and Methods. 15 obese patients with type 2 diabetes were studied, all using metformin (1-2 g/day) and sulfonylurea (glimiperide). All patients received L 1.2 mg daily add-on to stable therapy for 6 weeks. Blood samples were collected before, 6 weeks after start of treatment and after an overnight fast 6 weeks after stopping L, mononuclear cells (MNC) were isolated. The mRNA expressions of TNF-α, TLR2, TLR4, NOD1, IL-2 and SIRT1 were measured in MNC by RT-PCR. Ceruloplasmin concentration was measured in plasma by photometric method.Results. In this add-on pilot clinical investigation we received new data that L can inhibit proinflammatory NF-kB pathway by increased SIRT1 expression in obese patients with type 2 DM improving metabolic profile. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, and plasma ceruloplasmin fell after 6 weeks of L. Expressions of IL-2 and NOD-1 were stable. There was a significant increase of SIRT1 mRNA expression. The mRNA expression in MNC of TNF-α, IkB, TLR2, TLR4, NOD1, SIRT1 and ceruloplasmin concentrations did not reverse to baseline levels after 6 weeks stopping of L treatment. IL-2 expression decreased in comparison with basic level.Conclusions. L has a potent anti-inflammatory effect as do GLP-1 agonists due to inhibition of NF-kB pathways and up-regulate SIRT1 expression, down-regulating pro-inflammatory factors including cytokines (TNF-α), extra- and intracellular receptors (TLR2, TLR4), and inflammation markers such as ceruloplasmin. Long lasting effects of L can be mediated by epigenetic regulation of NF-kB pathway by SIRT-1.

Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes

Department of Internal Medicine No.3 with Phthisiology

Research Institute for Genetics and Immunological Grounds of Pathology and Pharmacogenetics

Romanian Journal of Internal Medicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Introduction. Liraglutide (L) is the analogue of human glucagon-like peptide 1 which stimulates glucose-dependent insulin secretion and can modify the level of...

Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes

Publicado en línea: 09 sept 2019

Páginas: 233 - 240

Recibido: 26 sept 2018

DOI: https://doi.org/10.2478/rjim-2019-0003

Palabras clave
glucagon-like peptide 1 (GLP-1), liraglutide, diabetes, obesity, NF-kB, SIRT1, mediators of inflammation

© 2019 Liudmyla G. Savchenko et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes

Publicado en línea: 09 sept 2019

Páginas: 233 - 240

Recibido: 26 sept 2018

DOI: https://doi.org/10.2478/rjim-2019-0003

Palabras claveglucagon-like peptide 1 (GLP-1), liraglutide, diabetes, obesity, NF-kB, SIRT1, mediators of inflammation

© 2019 Liudmyla G. Savchenko et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Palabras clave
glucagon-like peptide 1 (GLP-1), liraglutide, diabetes, obesity, NF-kB, SIRT1, mediators of inflammation