Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats

Yin, Weiqin; Xu, Shiqing; Wang, Zai; Liu, Honglin; Peng, Liang; Fang, Qing; Deng, Tingting; Zhang, Wenjian; Lou, Jinning

doi:10.1016/j.bbrc.2017.11.076

Cited by 47 publications

(30 citation statements)

References 29 publications

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“…GLP-1 receptor agonists (GLP-1 RA) are used in the metabolic control of obesity and T2DM patients because they enhance glucose-dependent insulin synthesis and secretion, proliferation of β-cells, inhibition of β-cells apoptosis, delay of gastric emptying and regulation of appetite by satiety-effects with body weight reduction [323][324][325]. GLP-1 RA reduces albuminuria and histological renal damage [326], and downregulates genes related to inflammation (NF-κB, TNF-α, MCP-1) [327], oxidative stress (Nox4 and subunits gp91phox, p22phox, p47phox) [328], de novo lipogenesis/lipotoxicity (SREBP-1; ABCA1) [329] and fibrosis (α-SMA, fibronectin, collagen I) [330]. These renoprotective effects observed in T2DM and CKD patients have been validated by four major clinical trials AWARD-7 [331], LEADER [332], SUSTAIN-6 [333] and ELIXA [334].…”

Section: Novel Antidiabetic Drugs With Anti-inflammatory Actions In Dnmentioning

confidence: 99%

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Rayego‐Mateos

Morgado‐Pascual

Opazo-Ríos

et al. 2020

IJMS

175

127

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Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

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Section: Novel Antidiabetic Drugs With Anti-inflammatory Actions In Dnmentioning

confidence: 99%

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Rayego‐Mateos

Morgado‐Pascual

Opazo-Ríos

et al. 2020

IJMS

175

127

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“…GLP-1R activation leads to stimulation of cyclic adenosine monophosphate-protein kinase A pathways, producing antioxidative effects; it, therefore, seems likely that GLP-1 protects the kidney from oxidative injury [40]. In the diabetic nephropathy rat model, GLP-1RA also downregulated expression of several inflammatory biomarkers in rats, such as tubulointerstitial tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1(MCP-1), collagen I, alpha-smooth muscle actin (α-SMA) and fibronectin, all reported to play a role in diabetic nephropathy, as well as ameliorating kidney tubules and tubulointerstitial lesions [70].…”

Section: Modulation Of Cyclic Adenosine Monophosphate-protein Kinase mentioning

confidence: 99%

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

Górriz

Soler

Navarro‐González

et al. 2020

JCM

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Type 2 diabetes mellitus (T2DM) represents the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESKD), and diabetic kidney disease (DKD) is a major cause of morbidity and mortality in diabetes. Despite advances in the nephroprotective treatment of T2DM, DKD remains the most common complication, driving the need for renal replacement therapies (RRT) worldwide, and its incidence is increasing. Until recently, prevention of DKD progression was based around strict blood pressure (BP) control, using renin–angiotensin system blockers that simultaneously reduce BP and proteinuria, adequate glycemic control and control of cardiovascular risk factors. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of anti-hyperglycemic drugs shown to improve cardiovascular and renal events in DKD. In this regard, GLP-1RA offer the potential for adequate glycemic control in multiple stages of DKD without an increased risk of hypoglycemia, preventing the onset of macroalbuminuria and slowing the decline of glomerular filtration rate (GFR) in diabetic patients, also bringing additional benefit in weight reduction, cardiovascular and other kidney outcomes. Results from ongoing trials are pending to assess the impact of GLP-1RA treatments on primary kidney endpoints in DKD.

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“…Consistent with this observation, liraglutide has been shown to attenuate unilateral ureteral obstruction (UUO)-induced tubulointerstitial fibrosis by suppressing TGF-β and its downstream signaling pathways, including Smad3 and ERK1/2 ( Li et al., 2018 ). These protective effects of GLP-1RAs for renal fibrosis are also mediated by attenuating the epithelial-to-mesenchymal transition (EMT) of tubular cells ( Li et al., 2018 ; Yin et al., 2018 ).…”

Section: Renoprotective Mechanisms Of Glp-1rasmentioning

confidence: 99%

GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Clinical Outcomes to Mechanisms

Kawanami

Yuasa

2020

Front. Pharmacol.

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Diabetic Kidney Disease (DKD) is the leading cause of end stage renal disease (ESRD) worldwide. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are now widely used in the treatment of patients with type 2 diabetes (T2D). A series of clinical and experimental studies demonstrated that GLP-1RAs have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by natriuresis, antiinflammatory and anti-oxidative stress properties. Furthermore, GLP-1RAs have been shown to suppress renal fibrosis. Recent clinical trials have demonstrated that GLP-1RAs have beneficial effects on renal outcomes, especially in patients with T2D who are at high risk for CVD. These findings suggest that GLP-1RAs hold great promise in preventing the onset and progression of DKD. However, GLP-1RAs have only been shown to reduce albuminuria, and their ability to reduce progression to ESRD remains to be elucidated. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying the effects of GLP-1RAs in DKD.

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Recombinant human GLP-1(rhGLP-1) alleviating renal tubulointestitial injury in diabetic STZ-induced rats

Cited by 47 publications

References 29 publications

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

GLP-1 Receptor Agonists and Diabetic Kidney Disease: A Call of Attention to Nephrologists

GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Clinical Outcomes to Mechanisms

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