Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells

Dorecka, Mariola; Siemianowicz, Krzysztof; Francuz, Tomasz; Garczorz, Wojciech; Chyra, Agnieszka; Kłych, Agnieszka; Romaniuk, W

doi:10.1016/s1734-1140(13)71069-7

Cited by 33 publications

(25 citation statements)

References 42 publications

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“…An in vitro study by Dorecka and colleagues [44] demonstrated that treatment with GLP-1 (100 nM) inhibited TNF-α-induced expression of receptors for advanced glycation end products (RAGE), ICAM-1 and VCAM-1 in cultured human retinal pigment epithelial cells, suggesting that attenuation of TNF-α might be a mechanism for the action of GLP1. In line with this conclusion, the present study found that TNF-α expression was attenuated at the level of mRNA in cardiac tissues by GLP1 treatment.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

et al. 2020

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The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups: (a) control group, (b) DM group, type 2 diabetic rats with saline daily for 4 weeks, (c) DM + GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 µg/kg for 4 weeks, and (d) DM + SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α, and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB, and LDH (p < 0.05). Also, DM caused significant myocardial damage and fibrosis; elevation of myocardial MDA; NE with upregulation of myocardial caspase-3, TNF-α, TGF-β, and TH; and significant decrease in serum insulin and myocardial GSH and CAT (p < 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p < 0.05). Conclusion: We concluded that both GLP1 and SGLT2i exhibited cardioprotective effects against DCM in T2DM, with the upper hand for SGLT2i. This might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and inflammatory cytokines (TNF-α and TGF-β).

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Section: Discussionmentioning

confidence: 99%

Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

et al. 2020

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“…In addition to these tissues, emerging data suggest that GLP-1-based therapies also showed anti-inflammatory effects on the liver, vascular system including aorta and vein endothelial cells, brain, kidney, lung, testis, and skin by reducing the production of inflammatory cytokines and infiltration of immune cells in the tissues [ 17 , 21 – 25 ]. Thus, GLP-1 therapy may be beneficial for the treatment of chronic inflammatory diseases including nonalcoholic steatohepatitis, atherosclerosis, neurodegenerative disorders, diabetic nephropathy, asthma, and psoriasis [ 14 , 26 – 32 ]. Drugs which are GLP-1 receptor agonists or DPP-4 inhibitors are shown in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

Lee

2016

Mediators of Inflammation

334

219

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Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammation in vivo and in vitro, and their molecular mechanisms of anti-inflammatory action.

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“…Further, vildagliptin treatment was found to completely inhibit the increase in angiogenic, inflammatory and thrombogenic gene expression (VEGF, ICAM-1 and PAI-1) in the retinas of OLETF rats [ 151 ]. Exendin-4 and GLP-1 decreased RAGE levels in AGEs-exposed human retinal pigment epithelial cells and made these cells more resistant to harmful effects of AGEs, leading to suppression of ICAM-1 and VCAM-1 levels [ 152 ], thus suggesting the clinical utility of DPP-4 inhibitors and/or GLP-1-based medicine for the treatment of obese type 2 diabetes, including diabetic retinopathy. The effects of DPP-4 inhibition on microvascular complications were recently thoroughly described by Avogaro [ 153 ].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications

Yamagishi

Fukami

Matsui

2015

Cardiovasc Diabetol

105

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Advanced glycation end products (AGEs) consist of heterogenous group of macroprotein derivatives, which are formed by non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids, and whose process has progressed at an accelerated rate under diabetes. Non-enzymatic glycation and cross-linking of protein alter its structural integrity and function, contributing to the aging of macromolecules. Furthermore, engagement of receptor for AGEs (RAGE) with AGEs elicits oxidative stress generation and subsequently evokes proliferative, inflammatory, and fibrotic reactions in a variety of cells. Indeed, accumulating evidence has suggested the active involvement of accumulation of AGEs in diabetes-associated disorders such as diabetic microangiopathy, atherosclerotic cardiovascular diseases, Alzheimer’s disease and osteoporosis. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins, gut hormones secreted from the intestine in response to food intake, both of which augment glucose-induced insulin release, suppress glucagon secretion, and slow gastric emptying. Since GLP-1 and GIP are rapidly degraded and inactivated by dipeptidyl peptidase-4 (DPP-4), inhibition of DPP-4 and/or DPP-4-resistant GLP-1 analogues have been proposed as a potential target for the treatment of diabetes. Recently, DPP-4 has been shown to cleave multiple peptides, and blockade of DPP-4 could exert diverse biological actions in GLP-1- or GIP-independent manner. This article summarizes the crosstalk between AGEs-RAGE axis and DPP-4-incretin system in the development and progression of diabetes-associated disorders and its therapeutic intervention, especially focusing on diabetic vascular complications.

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Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells

Cited by 33 publications

References 42 publications

Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control

Crosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications

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