Liraglutide exerts an anti-inflammatory action in obese patients with type 2 diabetes
| Autor: | Elvira I. Kaidasheva, O. A. Shlykova, Liudmyla G. Savchenko, L. E. Vesnina, Liudmyla G. Selikhova, Nataliia I. Digtiar, Igor Kaidashev |
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| Rok vydání: | 2018 |
| Předmět: |
Male
sirt1 Gene Expression Pilot Projects Type 2 diabetes 0302 clinical medicine Sirtuin 1 Nod1 Signaling Adaptor Protein Prospective Studies Internal medicine mediators of inflammation 0303 health sciences diabetes biology NF-kappa B food and beverages Ceruloplasmin Middle Aged Metformin 030220 oncology & carcinogenesis glucagon-like peptide 1 (glp-1) Drug Therapy Combination Female I-kappa B Proteins medicine.symptom medicine.drug Signal Transduction medicine.medical_specialty nf-kb Inflammation Proinflammatory cytokine 03 medical and health sciences Diabetes mellitus medicine Humans Hypoglycemic Agents Obesity RNA Messenger 030304 developmental biology Liraglutide business.industry Tumor Necrosis Factor-alpha fungi Type 2 Diabetes Mellitus medicine.disease RC31-1245 Actins Toll-Like Receptor 2 Toll-Like Receptor 4 Endocrinology Sulfonylurea Compounds Diabetes Mellitus Type 2 biology.protein Leukocytes Mononuclear Interleukin-2 business |
| Zdroj: | Romanian Journal of Internal Medicine, Vol 57, Iss 3, Pp 233-240 (2019) |
| ISSN: | 2501-062X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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