Differential Effects of Biologics on Psoriasis-Related Vascular Inflammation and Risk of Thrombosis
Programa Estatal de I+D+i Orientada a los Retos de la Sociedad from Ministerio de Ciencia, Innovación y Universidades and European Regional Development Fund (Spain) [RTI2018-094436-B-I00]; Ministerio de Sanidad y Consumo CIBERehd (Spain) [CB06/04/0071]; Generalitat Valenciana (Spain) [PROMETEO/2018/141]; Proyectos Grupos Emergentes [GV/2019/043]; and Universidad Europea (Spain) (2018/UEM32 and 2019/UEM29]. 8.551 JCR (2020) Q1, 4/69 Dermatology 1.951 SJR (2020) Q1, 54/438 Biochemistry No data IDR 2020 UEV
Does Metformin Modulate Endoplasmic Reticulum Stress and Autophagy in Type 2 Diabetic Peripheral Blood Mononuclear Cells?
Since type 2 diabetes (T2D) is associated with oxidative stress and metformin has been shown to exert a protective role against the said stress, we wondered whether metformin treatment might also modulate endoplasmic reticulum (ER) stress and autophagy in leukocytes of T2D patients. We studied 53 T2D patients (37 of whom had been treated with metformin 1700 mg for at least 1 year) and 30 healthy volunteers. Leukocytes from both groups of T2D patients exhibited increased protein levels of 78-kDa glucose-regulated protein (GRP78) with respect to controls, whereas activating transcription factor 6 (ATF6) was enhanced specifically in nonmetformin-treated T2D, and (s-xbp1) and phosphorylated euk…
Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome
// Mariona Jove 1, * , Irene Pradas 1, * , Alba Naudi 1, * , Susana Rovira-Llopis 2 , Celia Banuls 2 , Milagros Rocha 2 , Manuel Portero-Otin 1 , Antonio Hernandez-Mijares 2, 3, 4, # , Victor M. Victor 2, 5, # and Reinald Pamplona 1, # 1 Department of Experimental Medicine, Lleida University-Institute for Research in Biomedicine of Lleida (UdL-IRBLleida), 25198 Lleida, Spain 2 Foundation for the Promotion of Healthcare and Biomedical Research in the Valencian Community (FISABIO), Service of Endocrinology, University Hospital Dr. Peset, 46017 Valencia, Spain 3 Fundacion Investigacion Hospital Clinico Universitario/INCLIVA, Valencia University, 46010 Valencia, Spain 4 Department of Medicine, …
Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance.
ObjectiveOxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα).Design and methodsOur study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (n=41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O2 consum…
Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity
Abstract Objective In obese patients undergoing caloric restriction, there are several potential mechanisms involved in the improvement of metabolic outcomes. The present study further explores whether caloric restriction can modulate endoplasmic reticulum (ER) stress and mitochondrial function, as both are known to be mechanisms underlying inflammation and insulin resistance (IR) during obesity. Methods A total of 64 obese patients with BMI ≥35 kg/m2 underwent a dietary program consisting of 6 weeks of a very-low-calorie diet followed by 18 weeks of low-calorie diet. We evaluated changes in the metabolic and inflammatory markers -TNFα, hsCRP, complement component 3 (C3c), and retinol bindi…
Perspectives and Potential Applications of Mitochondria-Targeted Antioxidants in Cardiometabolic Diseases and Type 2 Diabetes
There is abundant evidence to suggest that mitochondrial dysfunction is a main cause of insulin resistance and related cardiometabolic comorbidities. On the other hand, insulin resistance is one of the main characteristics of type 2 diabetes, obesity, and metabolic syndrome. Lipid and glucose metabolism require mitochondria to generate energy, and when O2 consumption is low due to inefficient nutrient oxidation, there is an increase in reactive oxygen species, which can impair different types of molecules, including DNA, lipids, proteins, and carbohydrates, thereby inducing proinflammatory processes. Factors which contribute to mitochondrial dysfunction, such as mitochondrial biogenesis and…
Chronic consumption of an inositol-enriched carob extract improves postprandial glycaemia and insulin sensitivity in healthy subjects: A randomized controlled trial
Background & aims: Inositols are thought to be mediators of the insulin signalling pathway. We assessed the effects of inositols on glycaemic control in fasting and postprandial states and evaluated lipoprotein profile and LDL particle size in healthy population. Methods: A 12-week double-blind clinical trial was performed with forty healthy subjects administered either an inositol-enriched beverage (IEB) -containing 2.23 g of inositols in 250 ml- or a sucrose-sweetened beverage (SB) twice a day. Anthropometric measurements, fasting glucose levels, insulin and HOMA-IR index, lipoprotein profile and postprandial glucose concentrations (measured using the continuous glucose monitoring system …
Does Glycemic Control Modulate the Impairment of NLRP3 Inflammasome Activation in Type 2 Diabetes?
Since mitochondrial dysfunction is associated with NOD-like receptor family protein 3 (NLRP3) activation in type 2 diabetes (T2D), which can eventually lead to an impaired immune response, we set out to determine if glycemic control modulates the effects of T2D on the NLRP3 inflammasome. We have studied leukocytes from 61 diabetic patients [25 with glycated hemoglobin (HbA(1c)) 7% and 36 with HbA(1c) 8%] and 40 healthy controls. Total and mitochondrial reactive oxygen species (ROS) production was enhanced in T2D patients, and mitochondrial ROS was more pronounced in those with poor glycemic control. Levels of gene and protein expression of NLRP3 were decreased in both diabetic groups and mo…
Mitochondria, the NLRP3 Inflammasome, and Sirtuins in Type 2 Diabetes: New Therapeutic TargetsReviewing Editors:Markus Bachschmid, Dylan Burger, Vittorio Calabrese, Amadou Camara, Lukas Kubala, Giuseppe Poli, and Chandan K. Sen
Abstract Significance: Type 2 diabetes mellitus and hyperglycemia can lead to the development of comorbidities such as atherosclerosis and microvascular/macrovascular complications. Both type 2 dia...
Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?
Mitochondrial fusion/fission alterations have been evaluated in different tissues of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial dynamics is disturbed in the leukocytes of T2D patients and whether glycemic control affects its regulation. Anthropometric and metabolic parameters in 91 T2D patients (48 with glycated hemoglobin [HbA1c]6.5% and 43 with HbA1c6.5%) were characteristic of the disease when compared with 78 control subjects. We observed increased reactive oxygen species production in leukocytes from diabetic patients, together with a reduced mitochondrial oxygen consumption rate, especially in poorly controlled patients. Mitochondrial fusion was red…
The role of reactive oxygen species in obesity therapeutics.
Obesity is a major risk factor for multiple severe health conditions, including cardiovascular diseases, diabetes and cancer. It is often related to an increased risk of morbidity and mortality and, as it can be accompanied by non-fatal health problems, quality of life is seriously reduced due to related conditions including hypertension, sleep apnea, osteoarthritis, respiratory problems and infertility. Evidence suggests that oxidative stress is related to obesity and its complications. In obese patients, there is an increase in levels of reactive oxygen species and nitrogen species and antioxidant defenses are undermined in comparison to normal-weight counterparts. In addition, these para…
The consumption of a bread enriched with dietary fibre and l-carnitine improves glucose homoeostasis and insulin sensitivity in patients with metabolic syndrome
The aim of this study was to evaluate the efficacy of a bakery product enriched with dietary fibre and L-carnitine in countering glucose homoeostasis and insulin sensitivity in patients with and without MetS. This was a 12-week, double-blind, randomized placebo-controlled trial employing fifty-four subjects (28 with MetS and 26 without MetS). After one month (run-in period), subjects were divided into two intervention groups: one received dietary fibre (5.59 g of soluble fibre and 9.49 g of insoluble fibre) plus 2325 mg of L-carnitine enriched bread (n = 26) and the other received placebo bread (n = 28). Anthropometric measurements, biochemical parameters inflammatory markers and LDL subfra…
Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte–endothelium interactions in PCOS
Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions.This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endotheli…
Characterization of Differentially Expressed Circulating miRNAs in Metabolically Healthy versus Unhealthy Obesity
Obese individuals without metabolic comorbidities are categorized as metabolically healthy obese (MHO). MicroRNAs (miRNAs) may be implicated in MHO. This cross-sectional study explores the link between circulating miRNAs and the main components of metabolic syndrome (MetS) in the context of obesity. We also examine oxidative stress biomarkers in MHO vs. metabolically unhealthy obesity (MUO). We analysed 3536 serum miRNAs in 20 middle-aged obese individuals: 10 MHO and 10 MUO. A total of 159 miRNAs were differentially expressed, of which, 72 miRNAs (45.2%) were higher and 87 miRNAs (54.7%) were lower in the MUO group. In addition, miRNAs related to insulin signalling and lipid metabolism pat…
Involvement of leucocyte/endothelial cell interactions in anorexia nervosa.
Background Anorexia nervosa is a common psychiatric disorder in adolescence and is related to cardiovascular complications. Our aim was to study the effect of anorexia nervosa on metabolic parameters, leucocyte–endothelium interactions, adhesion molecules and proinflammatory cytokines. Materials and Methods This multicentre, cross-sectional, case–control study employed a population of 24 anorexic female patients and 36 controls. We evaluated anthropometric and metabolic parameters, interactions between leucocytes polymorphonuclear neutrophils (PMN) and human umbilical vein endothelial cells (HUVEC), proinflammatory cytokines such as tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL…
Metformin modulates human leukocyte/endothelial cell interactions and proinflammatory cytokines in polycystic ovary syndrome patients
Abstract Objective We aim to assess the effect of metformin treatment on metabolic parameters, endothelial function and inflammatory markers in polycystic ovary syndrome (PCOS) subjects. Methods The study population consisted of 40 reproductive-age women with PCOS, who underwent treatment with metformin during a 12-week period, and their corresponding matched controls (n = 44). We evaluated endocrinological parameters, adhesion molecules (vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1) and E-selectin) and proinflammatory cytokines (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα)) in serum. In addition, interactions between human umbili…
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF). PARKIN and (PTEN)-induced putative kinase 1 (PINK1) partici…
Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase
Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (…
Association of Serum Retinol Binding Protein 4 with Atherogenic Dyslipidemia in Morbid Obese Patients
Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m(2)) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9±14.6; 42.3±17.0 and 37.4±11.7 µg/ml, respectively) and corr…
Pinitol alleviates systemic inflammatory cytokines in human obesity by a mechanism involving unfolded protein response and sirtuin 1
Summary Background & aims It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). Methods In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the ex vivo study, a biopsy of VAT and SAT was removed from thirty-four obese patients and incubated with D-pinitol for 48 h. Results The consump…
The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients
It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA…
Effects of simvastatin, ezetimibe and simvastatin/ezetimibe on mitochondrial function and leukocyte/endothelial cell interactions in patients with hypercholesterolemia
Cholesterol-lowering therapy has been related with several beneficial effects; however, its influence on oxidative stress and endothelial function is not fully elucidated.To investigate the effect of simvastatin and ezetimibe on mitochondrial function and leukocyte-endothelium interactions in polymorphonuclear cells of hyperlipidemic patients.Thirty-nine hyperlipidemic patients were randomly assigned to one of two groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period. Lipid profile, mitochondrial parameters (oxygen consumption, reactive oxygen species (…
Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial ischemia.
OBJECTIVE Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed. RESEARCH DESIGN AND METHODS Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition– and age-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed. RESULTS Waist, levels of triglycerides, proinflammatory cytokines (i…
Oxidative and endoplasmic reticulum stress is impaired in leukocytes from metabolically unhealthy vs healthy obese individuals.
BACKGROUND: Oxidative stress and inflammation are related to obesity, but the influence of metabolic disturbances on these parameters and their relationship with endoplasmic reticulum (ER) stress is unknown. Therefore, this study was performed to evaluate whether metabolic profile influences ER and oxidative stress in an obese population with/without comorbidities. SUBJECTS AND METHODS: A total of 113 obese patients were enrolled in the study; 29 were metabolically healthy (MHO), 53 were metabolically abnormal (MAO) and 31 had type 2 diabetes (MADO). We assessed metabolic parameters, proinflammatory cytokines (TNF alpha and IL-6), mitochondrial and total reactive oxygen species (ROS) produc…
The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic β Cells Exposed to Hyperglycaemia.
Background/aims Mitochondria-targeted antioxidants such as mitoquinone (MitoQ) have demonstrated protective effects against oxidative damage in several diseases. The increase in reactive oxygen species (ROS) production during glucose metabolism in β cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to β cell function impairment. In the present work, we aimed to evaluate the effect of MitoQ on insulin secretion, oxidative stress, endoplasmic reticulum (ER) stress and nuclear factor kappa B (NFκB) signalling in a pancreatic β cell line under normoglycaemic (NG, 11.1 mM glucose), hyperglycaemic (HG, 25 mM glucose) and lipidic (palmitic ac…
Altered Mitochondrial Function and Oxidative Stress in Leukocytes of Anorexia Nervosa Patients
ContextAnorexia nervosa is a common illness among adolescents and is characterised by oxidative stress.ObjectiveThe effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated.Design and settingA multi-centre, cross-sectional case-control study was performed.PatientsOur study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women.Main outcome measuresAnthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumpt…
Effect of consumption of a carob pod inositol-enriched beverage on insulin sensitivity and inflammation in middle-aged prediabetic subjects.
This study assessed the effects of an inositol-enriched beverage (IEB) on blood glucose levels and inflammation status in subjects with an impaired fasting glucose (IFG) state according to body mass index (BMI). This was a 12 week, double-blind, randomized, controlled trial employing forty-four IFG subjects (fasting glucose levels 100-125 mg dl-1) that were divided into two intervention groups: one receiving a IEB (n = 24) containing mainly pinitol (2.0 g twice a day), and the other a sweetened beverage based on sucrose (SB; n = 20). Anthropometric and biochemical measurements, postprandial and fasting nocturnal glycaemia (continuous glucose monitoring system), and inflammatory parameters (…
Does Metformin Protect Diabetic Patients from Oxidative Stress and Leukocyte-Endothelium Interactions?
Since metformin can exert beneficial vascular effects, we aimed at studying its effect on reactive oxygen species (ROS) production, antioxidant enzyme expression, levels of adhesion molecules, and leukocyte-endothelium interactions in the leukocytes from type 2 diabetic (T2D) patients. The study was carried out in 72 T2D patients (41 of whom were treated with metformin for at least 12 months at a dose of 1700 mg per day), and in 40 sex- and age-matched control subjects. Leukocytes from T2D patients exhibited enhanced levels of mitochondrial ROS and decreased mRNA levels of glutathione peroxidase 1 (gpx1) and sirtuin 3 (sirt3) with respect to controls, whereas metformin was shown to revert t…
Is Myeloperoxidase a Key Component in the ROS-Induced Vascular Damage Related to Nephropathy in Type 2 Diabetes?
AbstractIt is still unclear whether microvascular complications of type 2 diabetes correlate with leukocyte-endothelium interactions and/or myeloperoxidase (MPO) levels. In the present study, we found that serum levels of glucose, the rate of ROS and MPO concentration were higher in type 2 diabetic patients. Patients with nephropathy (39.6%) presented higher MPO levels that correlate positively with the albumin/creatinine ratio (r=0.59, p<0.05). In addition, nephropatic patients showed increased leukocyte-endothelium interactions due to an undermining of polymorphonuclear leukocytes (PMN) rolling velocity and increased rolling flux and adhesion, which was accompanied by a rise in levels of …
Chronic consumption of an inositol-enriched beverage ameliorates endothelial dysfunction and oxidative stress in type 2 diabetes
The anti-diabetic properties of an inositol-enriched beverage (IEB) on the endothelial function and redox status in diabetic subjects were assessed. This was a 12-week, double-blind randomized controlled trial employing thirty-eight diabetic subjects that were divided into two intervention groups: one receiving an IEB and the other a sucrose-enriched beverage. Subjects consuming IEB exhibited a significant decrease in triacylglycerol (8.82%) and HbA1c (4.53%) levels. Continuous glucose monitoring revealed a significant net reduction of 2.51 and 7.11% during postprandial and overnight fasting periods after consumption of IEB, respectively. Moreover, IEB improved endothelial function by reduc…
Metformin induces lipid changes on sphingolipid species and oxidized lipids in polycystic ovary syndrome women.
Metformin is one of the treatments used for pcoS pathology decreasing body weight, plasma androgen, FSH and glucose levels. Unfortunately, there is little known about metformin’s effects on lipid metabolism, a crucial process in pcoS pathology. We have employed a lipidomic approach to explore alterations in the plasma lipid profile of patients with PCOS following metformin treatment. The aim is to offer new insights about the effect of metformin in PCOS patients. Plasma samples were obtained from 27 subjects prior to and following 12 weeks of metformin treatment. A detailed biochemical characterization and lipidomic profile was performed. Metformin reduces BMI, HOMA-IR, fSH and androstenedi…
Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients
Abstract Introduction Low testosterone levels in men are associated with type 2 diabetes and cardiovascular risk. However, the role of testosterone in mitochondrial function and leukocyte-endothelium interactions is unknown. Our aim was to evaluate the relationship between testosterone levels, metabolic parameters, oxidative stress, mitochondrial function, inflammation and leukocyte-endothelium interactions in type 2 diabetic patients. Materials and methods The study was performed in 280 male type 2 diabetic patients and 50 control subjects. Anthropometric and metabolic parameters, testosterone levels, reactive oxygen species (ROS) production, mitochondrial membrane potential, TNFα, adhesio…
The SGLT2 Inhibitor Empagliflozin Ameliorates the Inflammatory Profile in Type 2 Diabetic Patients and Promotes an Antioxidant Response in Leukocytes
Sodium&ndash
Downregulation of miR-31 in Diabetic Nephropathy and its Relationship with Inflammation
Background/Aims: There is a lack of reliable biological markers for the early diagnosis of diabetic nephropathy (DN) during type 2 diabetes. In this pilot study we aim to assess whether miR-31 levels are modulated by the presence of DN and whether the expression of this miRNA is related to leukocyte-endothelial interactions and inflammation. Methods: Thirty-one T2D patients were enrolled in this pilot study; 18 with no diabetic complications and 13 with diabetic nephropathy. 24 non-diabetic subjects and 13 T2D patients with retinopathy (absent of other complications) were included to test the specificity of miR-31. Following anthropometric and biochemical evaluation, serum miR-31 levels wer…
Is Autophagy Altered in the Leukocytes of Type 2 Diabetic Patients?
It is unknown whether autophagy is altered in the leukocytes of type 2 diabetes (T2D) patients and whether oxidative and endoplasmic reticulum (ER) stresses regulate this mechanism. We studied anthropometric and metabolic parameters and evaluated oxidative stress, chromatin condensation, ER stress, and autophagy parameters in leukocytes of 103 T2D patients versus 109 sex- and age-matched controls. Patients showed increases in glucose, insulin, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) compared with controls (p < 0.001). Leukocytes displayed enhanced total and mitochondrial reactive oxygen species (ROS), reduced mitochondrial mass, and increased chro…
The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes
AbstractThere is growing focus on mitochondrial impairment and cardiovascular diseases (CVD) in type 2 diabetes (T2D), and the development of novel therapeutic strategies in this context. It is unknown whether mitochondrial-targeting antioxidants such as SS-31 protect sufficiently against oxidative damage in diabetes. We aimed to evaluate if SS-31 modulates SIRT1 levels and ameliorates leukocyte-endothelium interactions, oxidative stress and inflammation in T2D patients. Anthropometric and metabolic parameters were studied in 51 T2D patients and 57 controls. Production of mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential, glutathione content, leukocyte-endotheliu…