scholarly journals The role of microparticles in pathomechanisms of diabetic retinopathy – analysis of intercellular communication mechanisms in endothelial aging. Case control study in patients with metabolic syndrome, diabetes type 1 and type 2

2014 ◽  
Vol 83 (4) ◽  
pp. 322-327
Author(s):  
Ewa Stępień ◽  
Iwona Szuścik ◽  
Aleksandra Tokarz ◽  
Francisco J. Enguita ◽  
Bogdan Solnica ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Diabetic Retinopathy ◽  
Diabetic Patients ◽  
Imaging Method ◽  
Membrane Glycoproteins

The project is proposed to explain the role of specific circulating microparticles (MPs) as conveyors in trafficking bio-active molecules in type 1 (T1DM) and type 2 (T2DM) diabetic patients with risk of diabetic retinopathy (DR) and in patients with metabolic syndrome (MS). The possible role of miRNAs as modulators of these processes (in switching on/off mechanism on the molecular level) is proposed. An increased number of MPs with respect to glucose concentrations and levels of proangiogenic factors in vivo (patients’ plasma) is expected. The relationship between age of patents and MP content (cell membrane glycoproteins, phosphatidylserine or miRNA profile) is possible. MPs will be obtained from T1DM (n = 30) T2DM (n = 30), MS (n = 30) and controls (n = 30). Retinopathy in diabetic patients will be assessed by imaging method. Biological profile of MPs will be assessed in vitro by means of flow cytometry, molecular biology methods and cell proliferation assays.

scholarly journals Distinct Gut Microbiota Induced by Different Fat-to-Sugar-Ratio High-Energy Diets Share Similar Pro-obesity Genetic and Metabolite Profiles in Prediabetic Mice

mSystems ◽  
2019 ◽  
Vol 4 (5) ◽  
Author(s):  
Kai Shan ◽  
Hongyan Qu ◽  
Keru Zhou ◽  
Liangfang Wang ◽  
Congmin Zhu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Early Stage ◽  
Amplicon Sequencing ◽  
High Energy ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients

ABSTRACT Gut microbiota play important roles in host metabolism, especially in diabetes. However, why different diets lead to similar diabetic states despite being associated with different microbiota is not clear. Mice were fed two high-energy diets (HED) with the same energy density but different fat-to-sugar ratios to determine the associations between the microbiota and early-stage metabolic syndrome. The two diets resulted in different microbiota but similar diabetic states. Interestingly, the microbial gene profiles were not significantly different, and many common metabolites were identified, including l-aspartic acid, cholestan-3-ol (5β, 3α), and campesterol, which have been associated with lipogenesis and inflammation. Our study suggests that different metabolic-syndrome-inducing diets may result in different microbiota but similar microbiomes and metabolomes. This suggests that the metagenome and metabolome are crucial for the prognosis and pathogenesis of obesity and metabolic syndrome. IMPORTANCE Various types of diet can lead to type 2 diabetes. The gut microbiota in type 2 diabetic patients are also different. So, two questions arise: whether there are any commonalities between gut microbiota induced by different pro-obese diets and whether these commonalities lead to disease. Here we found that high-energy diets with two different fat-to-sugar ratios can both cause obesity and prediabetes but enrich different gut microbiota. Still, these different gut microbiota have similar genetic and metabolite compositions. The microbial metabolites in common between the diets modulate lipid accumulation and macrophage inflammation in vivo and in vitro. This work suggests that studies that only use 16S rRNA amplicon sequencing to determine how the microbes respond to diet and associate with diabetic state are missing vital information.

scholarly journals Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications

2021 ◽  
Vol 7 (3) ◽  
pp. 39
Author(s):  
Stanislovas S. Jankauskas ◽  
Jessica Gambardella ◽  
Celestino Sardu ◽  
Angela Lombardi ◽  
Gaetano Santulli
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Stress ◽  
Serum Levels ◽  
In Vitro Models ◽  
Preclinical Studies

Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the islets of Langerhans under metabolic stress. Moreover, miR-155 was shown to regulate insulin sensitivity in liver, adipose tissue, and skeletal muscle. Dysregulation of miR-155 expression was also shown to predict the development of nephropathy, neuropathy, and retinopathy in DM. Here, we systematically describe the reports investigating the role of miR-155 in DM and its complications. We also discuss the recent results from in vivo and in vitro models of type 1 diabetes (T1D) and T2D, discussing the differences between clinical and preclinical studies and shedding light on the molecular pathways mediated by miR-155 in different tissues affected by DM.

scholarly journals Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Satu Vavuli ◽  
Tuire Salonurmi ◽  
Sirpa Loukovaara ◽  
Antti E. Nissinen ◽  
Markku J. Savolainen ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Oxidized Ldl ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 1 Diabetic Patients ◽  
Type 2 Diabetic

Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p=0.001), and 76.1 (48.2) for NoDR (p=0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p=0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p>0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.

scholarly journals Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy

2021 ◽  
Vol 22 (8) ◽  
pp. 4020
Author(s):  
Enrique Antonio Alfonso-Muñoz ◽  
Raquel Burggraaf-Sánchez de las Matas ◽  
Jorge Mataix Boronat ◽  
Julio César Molina Martín ◽  
Carmen Desco
Keyword(s):  
Diabetic Retinopathy ◽  
Diabetic Macular Oedema ◽  
Complementary Therapy ◽  
Antioxidant Supplementation ◽  
Current Management ◽  
Adult Type ◽  
Aged People

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

scholarly journals Differential Activation of CD8+Tumor-Specific Tc1 and Tc2 Cells by an IL-10-Producing Murine Plasmacytoma

1998 ◽  
Vol 6 (3-4) ◽  
pp. 331-342 ◽  
Author(s):  
Christoph Specht ◽  
Hans-Gerd Pauels ◽  
Christian Becker ◽  
Eckehart Kölsch
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
T Cell Subsets ◽  
Early Stages ◽  
Specific Tolerance

The involvement of counteractiveCD8+T-cell subsets during tumor-specific immune responses was analyzed in a syngeneic murine plasmacytoma model.CD8+Tc cells against the immunogenic IL-10-producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced by immunization of BALB/c mice with X-irradiated ADJ-PC-5 tumor cellsin vivoandin vitro. However, the failure of recipient mice to mount a protective Tc response against the tumor during early stages of a real or simulated tumor growth is not due to immunological ignorance, but depends on the induction of tumor-specific tolerance, involving a population of tumorinducedCD8+T cells that are able to inhibit the generation of tumor-specific Tc cells in a primary ADJ-PC-5-specific MLTC, using IFN-γas a suppressive factor. Whereas most longterm cultivated CD8+ADJ-PC-5-specific Tc lines produce type-1 cytokines on stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum. Furthermore, the primaryin vitroTc response against ADJ-PC-5 cells shows characteristics of a Tc2 response. The Tc response is strictly depending on tumor-derived IL-10.CD8+Tc cells that are induced in a primary MLTC do not produce IFN-γ, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-γor IL-12. In contrast, ADJ-PC- 5-specificCD8+Tc cells from immunized mice are IFN-γproducing Tc1 cells. Since the primaryin vitroTc response against the tumor is suppressed even by the smallest numbers of irradiated ADJ-PC-5-specific Tc1 cells via IFN-γthese Tc1 cells behave similar to the suppressiveCD8+T cells that are induced during early stages of ADJ-PC-5 tumorigenesis.

Stem Cell Therapy for T1 D and T2 D Diabetic patients

2020 ◽  
Vol 11 (10) ◽  
pp. 23-25
Author(s):  
Nandakumar Ravichandran
Keyword(s):  
Diabetic Retinopathy ◽  
Beta Cells ◽  
Chronic Condition ◽  
Major Complication ◽  
Limb Ischemia ◽  
Diabetic Patients ◽  
Insulin Production ◽  
Working Age

Diabetes is a chronic condition that causes several diseases. Type 1 and Type 2 dependent diabetes are shown more concern in today’s world. Type1 dependent patients suffers from inability of the Beta cells to produce insulin whereas Type 2 dependent patients suffers from insufficient insulin production. Diabetic Retinopathy, Nephropathy, Critical Limb Ischemia and impaired glucose tolerance are some of the major risk factors of Diabetes. Diabetic Retinopathy is a major complication of Diabetes causing blindness in working age adults. This article discusses some research methods involved in the generation of Beta cells carried out by certain authors, hypothesis and future works in this field.

scholarly journals Enhanced phosphorylation of Na+–Cl− co-transporter in experimental metabolic syndrome: role of insulin

2012 ◽  
Vol 123 (11) ◽  
pp. 635-647 ◽  
Author(s):  
Radko Komers ◽  
Shaunessy Rogers ◽  
Terry T. Oyama ◽  
Bei Xu ◽  
Chao-Ling Yang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Endogenous Expression ◽  
The Metabolic Syndrome ◽  
Mammalian Cell Lines ◽  
Phosphoinositide 3 Kinase

In the present study, we investigated the activity of the thiazide-sensitive NCC (Na+–Cl− co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12-week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL (Zucker lean) control animals, together with renal NCC expression and molecular markers of NCC activity, such as localization and phosphorylation. Effects of insulin were studied further in mammalian cell lines with inducible and endogenous expression of this molecule. ZO rats displayed marked hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ were enhanced compared with ZL rats, and were associated with a decrease in BP (blood pressure). ZO rats displayed enhanced Thr53 NCC phosphorylation and predominant membrane localization of both total and phosphorylated NCC, together with a different profile in expression of SPAK (Ste20-related proline/alanine-rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase) inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but delayed compared with the time course of NCC phosphorylation. In summary, we report increased NCC activity in hyperinsulinaemic rodents in conjunction with the SPAK expression profile consistent with NCC activation and reduced WNK4, as well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro. Together, these findings indicate that hyperinsulinaemia is an important driving force of NCC activity in the metabolic syndrome with possible consequences for BP regulation.

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study

2019 ◽  
Vol 105 (4) ◽  
pp. e1549-e1560 ◽  
Author(s):  
Bénédicte Gaborit ◽  
Jean-Baptiste Julla ◽  
Samaher Besbes ◽  
Matthieu Proust ◽  
Clara Vincentelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Fundus Photography ◽  
Endothelial Cell Proliferation ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Aims Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. Methods We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs. We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. Results In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800–1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. Conclusions The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

scholarly journals PPARδActivity in Cardiovascular Diseases: A Potential Pharmacological Target

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Tesse ◽  
Ramaroson Andriantsitohaina ◽  
Thierry Ragot
Keyword(s):  
Metabolic Diseases ◽  
Peroxisome Proliferator ◽  
In Vivo Models ◽  
Pharmacological Target ◽  
Cardiovascular Cells ◽  
Peroxisome Proliferator Activated Receptors

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARαand PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARαand PPARγanti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδin cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδselective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδactivation. Recent reports suggest that the PPARδactivation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

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