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

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 protects against high-fat diet-induced kidney injury by ameliorating apoptosis

“…In podocyte-specific Sirt1 knockout diabetic nephropathy mouse model, proteinuria increases significantly as compared to diabetic nephropathy mouse ( 41 ). Several studies have demonstrated that SIRT1 plays a positive role via the action of GLP-1 on maintaining glucose homeostasis ( 42 , 43 ). The effect of exenatide on maintaining glucose homeostasis and improving insulin sensibility was attenuated in SIRT1 +/− mice fed with HFD ( 42 ).…”

“…The effect of exenatide on maintaining glucose homeostasis and improving insulin sensibility was attenuated in SIRT1 +/− mice fed with HFD ( 42 ). Liraglutide exerts a potent anti-inflammatory effect due to the inhibition of NF-κB pathway and upregulated level of SIRT1 in blood samples of patients with obesity and T2DM ( 43 ). Another study showed that SIRT1 and thioredoxin-interacting protein (TXNIP) have opposite effects on oxidative stress and metabolism in mediating the anti-aging interventions ( 44 ).…”

Anti-Proliferative Activity of Glucagon-Like Peptide-1 Receptor Agonist on Obesity-Associated Breast Cancer: The Impact on Modulating Adipokines’ Expression in Adipocytes and Cancer Cells

“…12,16,41 Our study showed that LG ameliorated the significant high levels of IL-6 and TNF-α produced from obese ADSCs suggesting the association of anti-inflammatory effects with its anti-proliferative efficacy in obese conditions. Recent studies proved the potent anti-inflammatory effect of LG in obese diabetic patients 37 and in obesity-related glomerulopathy 43 via down-regulation of pro-inflammatory factors including TNF-α and IL-6.…”

“…35 LG causes both upregulation of adiponectin and anti-inflammatory effect in diabetic patients. 36,37 Although the anti-proliferative activity of LG has been reported on human prostate 31 and pancreatic 32 cancers as well as in hepatocellular carcinoma cells, 33 it is unknown whether LG could exert anti-proliferative effects against BC, particularly in obese subjects. According to previously mentioned data, we hypothesize that treatment with LG may mitigate the BC growth in obese subjects and this effect is mediated via modulating the secretion of leptin, adiponectin and inflammatory cytokines from ADSCs and cancer cells…”

Can We Decrease Epicardial and Pericardial Fat in Patients With Diabetes?

“…164 Liraglutide had an anti-inflammatory effect due to inhibition of NF-kB pathways, down-regulating TNF-α. 165 In addition, treatment with liraglutide improved adiponectin levels. 166…”