Inflammation in obesity, diabetes, and related disorders

Immunity, Journal Year: 2022, Volume and Issue: 55(1), P. 31 - 55

Published: Jan. 1, 2022

Language: Английский

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Emerging Targets in Type 2 Diabetes and Diabetic Complications

Advanced Science, Journal Year: 2021, Volume and Issue: 8(18)

Published: July 28, 2021

Abstract Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although large drug portfolio exists to keep the levels under control, these medications are not without side effects. More importantly, once diagnosed rarely reversible. Dysfunctions in kidney, retina, cardiovascular system, neurons, liver represent common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, molecular mechanisms how type develops leads irreparable damage remain elusive. This review particularly focuses on novel targets may play role pathogenesis diabetes. Further research eventually pave way for treatment—or even prevention—of along with its complications.

Language: Английский

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VEGFR1 signaling in retinal angiogenesis and microinflammation

Progress in Retinal and Eye Research, Journal Year: 2021, Volume and Issue: 84, P. 100954 - 100954

Published: Feb. 26, 2021

Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, –C, -D, and placental [PlGF]) constitute the VEGF family. VEGF-A binds receptors 1 2 (VEGFR1/2), whereas VEGF-B PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown importance involvement of VEGFR1 family angiogenesis, permeability, microinflammatory cascades within retina. Expression depends microenvironment, is differentially regulated under hypoxic inflammatory conditions, it detected choroidal cells, pericytes, mononuclear phagocytes (including microglia), Müller photoreceptor pigment epithelium. Whilst decoy function well established, consequences direct signaling are less clear. activation can affect permeability induce macrophage microglia production proinflammatory proangiogenic mediators. However ability PlGF, VEGF-B) compete against each other for binding heterodimerize complicates our understanding relative contribution alone toward pathologic processes seen diabetic retinopathy, occlusions, retinopathy prematurity, age-related macular degeneration. Clinically, anti-VEGF drugs proven transformational these pathologies their impact modulation still an opportunity-rich field further research.

Language: Английский

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Inflammatory and angiogenic biomarkers in diabetic retinopathy

Biochemia Medica, Journal Year: 2020, Volume and Issue: 30(3), P. 385 - 399

Published: July 31, 2020

Diabetic retinopathy (DR) is one of the most common microvascular complications diabetes mellitus (DM) and a leading cause blindness in working-age adults developed countries. Numerous investigations have recognised inflammation angiogenesis as important factors development this complication diabetes. Current methods DR treatment are predominantly used at advanced stages disease could be associated with serious side effects. Therefore, new diagnostic needed order to identify initial well monitoring effects applied therapy. Biochemical biomarkers molecules found blood or other biological fluid tissue that indicate existence an abnormal condition disease. They valuable tool detecting early DR, identifying patients susceptible progression outcomes. Biomarkers related can measured blood, retina, vitreous, aqueous humour recently tears. As retina represents small part total body mass, circulating biomarker for needs highly specific. Local more reliable indicators retinal pathology; however, obtaining sample humour, vitreous invasive procedure potential complications. non-invasive novel method, tear analysis offers promising direction further research detection. The aim paper review systemic local inflammatory angiogenic relevant sight threatening diabetic complication.

Language: Английский

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Endothelial Dysfunction in Diabetic Retinopathy

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 4, 2020

Diabetic retinopathy (DR) is a diabetic complication which affects retinal function and results in severe loss of vision relevant diseases. Retinal vascular dysfunction caused by multi-factors, such as advanced glycosylation end products receptors, pro-inflammatory cytokines chemokines, proliferator‐activated receptor-γ disruption, growth factors, oxidative stress, microRNA etc. These factors promote endothelial the development DR. In this review, we summarize contributors pathophysiology DR for better understanding molecular cellular mechanism with special emphasis on dysfunction.

Language: Английский

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Causes and consequences of baseline cerebral blood flow reductions in Alzheimer’s disease

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2021, Volume and Issue: 41(7), P. 1501 - 1516

Published: Jan. 14, 2021

Reductions of baseline cerebral blood flow (CBF) ∼10–20% are a common symptom Alzheimer’s disease (AD) that appear early in progression and correlate with the severity cognitive impairment. These CBF deficits replicated mouse models AD recent work shows increasing can rapidly improve performance mice on short term memory tasks. Despite potential role these data suggest for reductions causing symptoms contributing to brain pathology AD, there remains poor understanding molecular cellular mechanisms them. This review compiles correlation AD-related comorbidities (e.g. cardiovascular genetic risk factors) outcomes pathology) from studies both patients models, discusses several proposed contribute reductions, based primarily models. Future research aimed at improving our importance interplay between different reduction, as well determining play could guide development future therapies target AD.

Language: Английский

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Anti-Inflammatory Strategies Targeting Metaflammation in Type 2 Diabetes

Molecules, Journal Year: 2020, Volume and Issue: 25(9), P. 2224 - 2224

Published: May 9, 2020

One of the concepts explaining coincidence obesity and type 2 diabetes (T2D) is metaflammation theory. This chronic, low-grade inflammatory state originating from metabolic cells in response to excess nutrients, contributes development T2D by increasing insulin resistance peripheral tissues (mainly liver, muscles, adipose tissue) targeting pancreatic islets this way impairing secretion. Given role not related infection inflammation both: insulitis, anti-inflammatory strategies could be helpful only control symptoms but also treat its causes. review presents current regarding obese individuals as well data concerning possible application different (including lifestyle interventions, extra-glycemic potential classical antidiabetic compounds, nonsteroidal drugs, immunomodulatory therapies, bariatric surgery) management T2D.

Language: Английский

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Dapagliflozin Reduces Apoptosis of Diabetic Retina and Human Retinal Microvascular Endothelial Cells Through ERK1/2/cPLA2/AA/ROS Pathway Independent of Hypoglycemic

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 24, 2022

Introduction: It is known that the metabolic disorder caused by high glucose one of pathogenesis in diabetic retinopathy (DR), leading cause blindness, due to main pathological change apoptosis endothelial cells (ECs). In previous studies, potential impact sodium cotransporter-2 (SGLT-2), whose inhibitors slow progression DR, has not been elucidated. The purpose presented study was explore effect SGLT-2 dapagliflozin (DAPA) on mice retina and human retinal microvascular (HRMECs), examine effects HRMECs metabolism, molecular processes affect DR. Methods Results: eyeballs male streptozotocin (STZ)-induced C57BL/6N were evaluated. divided into control group (CON), untreated (DM), treatment (DM + DAPA) insulin INS). Hematoxylin-Eosin (HE) staining performed observe structure retina, TUNEL detect cells. vitro, DCFH-DA western blot (WB) used evaluate ROS, Bcl-2, BAX, cleaved-caspase 3 metabolomics detected metabolism HRMECs. And then, we correlation analysis verification functions for significantly different metabolites. vivo, reduced independently hypoglycemic. protein expressed Dapagliflozin level ROS glucose, decreased expression cleaved-caspase3 ratio BAX/Bcl-2. Metabolomics results showed did intracellular level. Compared with group, production arachidonic acid (AA) inhibited phosphorylation ERK1/2, therefore, reducing cPLA2, which a key enzyme release. Conclusion: Collectively, unearthed first time induced DM whether vivo or vitro. uptake while mitigated alleviated through ERK/1/2/cPLA2/AA/ROS pathway.

Language: Английский

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Effects of inflammation on myopia: evidence and potential mechanisms

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 2, 2023

As the most common type of refractive error, myopia has become one leading causes visual impairment. With increasing prevalence myopia, there is a growing need to better understand factors involved in its development. Inflammation, fundamental pathophysiological processes humans, rapid response triggered by harmful stimuli and conditions. Although controlled inflammatory responses are necessary, over-activated inflammation soil for many diseases. The impact on received rising attention recent years. Elevated may contribute progression either directly or indirectly inducing scleral remodeling, development also increase ocular inflammation. This article provides comprehensive review interplay between potential biological mechanisms, which present new targets understanding pathology developing therapies.

Language: Английский

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The Role of Müller Cells in Diabetic Macular Edema

Investigative Ophthalmology & Visual Science, Journal Year: 2023, Volume and Issue: 64(10), P. 8 - 8

Published: July 7, 2023

Diabetic macular edema (DME) is a common complication of diabetic retinopathy and the leading cause vision loss in patients. Various factors, such as metabolic disorders inflammation caused by hyperglycemia, are involved occurrence development DME, but specific mechanism still unclear. Müller cells type macroglial cell unique to fundus, distributed throughout retina, they play role retinal homeostasis. This article reviews pathological process DME research progress treatment targeting through gene therapy.

Language: Английский

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