scholarly journals Glucagon-like peptide-1 and vitamin D: anti-inflammatory response in diabetic kidney disease in db/db mice and in cultured endothelial cells

2016 ◽  
Vol 32 (8) ◽  
pp. 805-815 ◽  
Author(s):  
Yael Einbinder ◽  
Meital Ohana ◽  
Sydney Benchetrit ◽  
Tania Zehavi ◽  
Naomi Nacasch ◽  
...  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Neil G. Docherty ◽  
Carel W. Le Roux

Diabetic kidney disease in patients with type 2 diabetes strongly correlates with the incidence of major cardiovascular events and all-cause mortality. Pharmacological and lifestyle based management focusing on glycaemic, lipid, and blood pressure control is the mainstay of treatment but efficacy remains limited. Roux en Y gastric bypass is an efficacious intervention in diabetes. Emerging evidence also supports a role for bypass as an intervention for early diabetic kidney disease. This paper firstly presents level 1 evidence of the effects of bypass on hyperglycaemia and hypertension and then summarises emerging data on its effects on diabetic kidney disease. Glucagon-like peptide-1 is implicated as a central mediator of diabetes resolution following bypass through the incretin effect. It has been ascribed vasodilatory, pronatriuretic, and antioxidant properties and its exogenous administration or optimisation of its endogenous levels via dipeptidyl peptidase IV inhibition results in antioxidant and antiproteinuric effects in preclinical models of DKD. Some evidence is emerging of translation of coherent effects in the clinical setting. These findings raise the question of whether pharmacotherapy targeted at optimising circulating hormone levels may be capable of recapitulating some of the effects of bypass surgery on renal injury.


2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii223-iii223
Author(s):  
Tali Zitman-Gal ◽  
Meital Ohana ◽  
Yael Einbinder ◽  
Jacques Bernheim ◽  
Sydney Benchetrit

2018 ◽  
Vol 315 (6) ◽  
pp. F1519-F1525 ◽  
Author(s):  
Brad P. Dieter ◽  
Radica Z. Alicic ◽  
Katherine R. Tuttle

Diabetic kidney disease (DKD), one of the most common and severe microvascular complications of diabetes, is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Since the development of renin-angiotensin system inhibition nearly three decades ago, no new therapeutic agents have received regulatory approval for treatment of DKD. Glucagon-like peptide-1 (GLP-1) receptor agonists, a class of newer antihyperglycemic agents, have shown promise for prevention of DKD onset and progression. This perspective summarizes clinical and experimental observations to give insight into biological mechanisms beyond glycemic control, such as natriuresis and anti-inflammatory actions, for preservation of kidney function in patients with diabetes.


2008 ◽  
Vol 105 (1) ◽  
pp. 260-265 ◽  
Author(s):  
Daniella Markovitch ◽  
Rex M. Tyrrell ◽  
Dylan Thompson

Strenuous exercise induces an initial pro- and subsequent anti-inflammatory response, and it has been suggested that this may be one of the ways that regular exercise reduces chronic inflammation and therefore the risk of cardiovascular disease. However, public health recommendations emphasize moderate-intensity physical activity, and it is important to understand whether moderate-intensity exercise has a similar anti-inflammatory effect. Twelve sedentary male volunteers (age 54 ± 4 yr) completed two main trials, moderate-intensity exercise and rest (30 min at 50% maximal oxygen uptake vs. sitting, respectively). There were no significant changes in circulating neutrophils, lymphocytes, monocytes, or serum interleukin-6, interleukin-10, and C-reactive protein concentration over the 7 days following exercise. Similarly, lymphocyte adhesion to cultured endothelial cells and heme oxygenase-1 (HO-1) expression in lymphocytes and monocytes were not affected by walking at any time point. These results suggest that the long-term anti-inflammatory and antiatherogenic effects of regular moderate-intensity physical activity must be explained by something other than a profound net anti-inflammatory response to each exercise bout since a single bout of walking did not lead to a change in various markers of inflammation or lymphocyte adherence to cultured endothelial cells.


2019 ◽  
Vol 30 (4) ◽  
pp. 546-562 ◽  
Author(s):  
Quan Hong ◽  
Lu Zhang ◽  
Jia Fu ◽  
Divya A. Verghese ◽  
Kinsuk Chauhan ◽  
...  

BackgroundGlomerular endothelial dysfunction and neoangiogenesis have long been implicated in the pathogenesis of diabetic kidney disease (DKD). However, the specific molecular pathways contributing to these processes in the early stages of DKD are not well understood. Our recent transcriptomic profiling of glomerular endothelial cells identified a number of proangiogenic genes that were upregulated in diabetic mice, including leucine-rich α-2-glycoprotein 1 (LRG1). LRG1 was previously shown to promote neovascularization in mouse models of ocular disease by potentiating endothelial TGF-β/activin receptor-like kinase 1 (ALK1) signaling. However, LRG1’s role in the kidney, particularly in the setting of DKD, has been unclear.MethodsWe analyzed expression of LRG1 mRNA in glomeruli of diabetic kidneys and assessed its localization by RNA in situ hybridization. We examined the effects of genetic ablation of Lrg1 on DKD progression in unilaterally nephrectomized, streptozotocin-induced diabetic mice at 12 and 20 weeks after diabetes induction. We also assessed whether plasma LRG1 was associated with renal outcome in patients with type 2 diabetes.ResultsLRG1 localized predominantly to glomerular endothelial cells, and its expression was elevated in the diabetic kidneys. LRG1 ablation markedly attenuated diabetes-induced glomerular angiogenesis, podocyte loss, and the development of diabetic glomerulopathy. These improvements were associated with reduced ALK1-Smad1/5/8 activation in glomeruli of diabetic mice. Moreover, increased plasma LRG1 was associated with worse renal outcome in patients with type 2 diabetes.ConclusionsThese findings identify LRG1 as a potential novel pathogenic mediator of diabetic glomerular neoangiogenesis and a risk factor in DKD progression.


2012 ◽  
Vol 9 (1) ◽  
pp. 6-7 ◽  
Author(s):  
Peter Rossing ◽  
Christel Joergensen

2019 ◽  
Vol 20 (20) ◽  
pp. 5101 ◽  
Author(s):  
Angelo Di Vincenzo ◽  
Claudio Tana ◽  
Hamza El Hadi ◽  
Claudio Pagano ◽  
Roberto Vettor ◽  
...  

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.


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