scholarly journals Dimethyl-2-oxoglutarate improves redox balance and mitochondrial function in muscle pericytes of individuals with diabetes mellitus

Diabetologia ◽  
2020 ◽  
Vol 63 (10) ◽  
pp. 2205-2217 ◽  
Author(s):  
Ashton Faulkner ◽  
Anita Tamiato ◽  
William Cathery ◽  
Andrea Rampin ◽  
Carlo Maria Caravaggi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Mitochondrial Function ◽  
Myogenic Differentiation ◽  
Tricarboxylic Acid Cycle ◽  
Antioxidant Properties ◽  
Vascular Complications ◽  
Redox Balance ◽  
Metabolic Enzyme ◽  
Antioxidant Systems ◽  
Limb Muscles

Abstract Aims/hypothesis Treatment of vascular complications of diabetes remains inadequate. We reported that muscle pericytes (MPs) from limb muscles of vascular patients with diabetes mellitus display elevated levels of oxidative stress causing a dysfunctional phenotype. Here, we investigated whether treatment with dimethyl-2-oxoglutarate (DM-2OG), a tricarboxylic acid cycle metabolite with antioxidant properties, can restore a healthy metabolic and functional phenotype. Methods MPs were isolated from limb muscles of diabetes patients with vascular disease (D-MPs) and from non-diabetic control participants (ND-MPs). Metabolic status was assessed in untreated and DM-2OG-treated (1 mmol/l) cells using an extracellular flux analyser and anion-exchange chromatography–mass spectrometry (IC-MS/MS). Redox status was measured using commercial kits and IC-MS/MS, with antioxidant and metabolic enzyme expression assessed by quantitative RT-PCR and western blotting. Myogenic differentiation and proliferation and pericyte–endothelial interaction were assessed as functional readouts. Results D-MPs showed mitochondrial dysfunction, suppressed glycolytic activity and reduced reactive oxygen species-buffering capacity, but no suppression of antioxidant systems when compared with ND-MP controls. DM-2OG supplementation improved redox balance and mitochondrial function, without affecting glycolysis or antioxidant systems. Nonetheless, this was not enough for treated D-MPs to regain the level of proliferation and myogenic differentiation of ND-MPs. Interestingly, DM-2OG exerted a positive effect on pericyte–endothelial cell interaction in the co-culture angiogenesis assay, independent of the diabetic status. Conclusions/interpretation These novel findings support the concept of using DM-2OG supplementation to improve pericyte redox balance and mitochondrial function, while concurrently allowing for enhanced pericyte–endothelial crosstalk. Such effects may help to prevent or slow down vasculopathy in skeletal muscles of people with diabetes.

scholarly journals The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 172 ◽  
Author(s):  
Adriana Elena Bulboaca ◽  
Paul-Mihai Boarescu ◽  
Alina Silvia Porfire ◽  
Gabriela Dogaru ◽  
Cristina Barbalata ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Capacity ◽  
Antioxidant Properties ◽  
Vascular Complications ◽  
Epigallocatechin Gallate ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Oxidative Stress Parameters ◽  
Stress Parameters

Background: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. Method: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1—control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2—STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3—STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4—STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). Results: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). Conclusions: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.

scholarly journals The Hepatoprotective Effect of Jaboticaba Peel Powder in a Rat Model of Type 2 Diabetes Mellitus Involves the Modulation of Thiol/Disulfide Redox State through the Upregulation of Glutathione Synthesis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Andréia Quatrin ◽  
Lisiane Conte ◽  
Dariane Trivisiol da Silva ◽  
Cassieli Gehlen Figueiredo ◽  
Sabrina Somacal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Antioxidant Properties ◽  
Redox Balance ◽  
Diabetic Rats ◽  
Hepatic Damage ◽  
Glutathione Synthesis

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzymeδ-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

An Overview of Nano formulated Nutraceuticals and its therapeutic approaches

2020 ◽  
Vol 16 ◽  
Author(s):  
Shaoli De ◽  
Agraharam Gopikrishna ◽  
Vedhantham Keerthana ◽  
Agnishwar Girigoswami ◽  
Koyeli Girigoswami
Keyword(s):  
Diabetes Mellitus ◽  
Food Habits ◽  
Health Effect ◽  
Antioxidant Properties ◽  
Therapeutic Approaches ◽  
Nutraceutical Compounds ◽  
Current Review ◽  
The People ◽  
Lifestyle Diseases ◽  
Herbal Formulations

Background: Economic development and vast changes in food habits have accelerated the consumption of junk foods which are the leading causes of several disorders that turns majority of the people to use various herbal formulations or drugs for preventing various lifestyle diseases. Nutraceuticals are the borderline apparatus between nutrients and drugs that provides supplementation of particular nutrient with favorable health effect. Objective: Various nutraceutical compounds like vitamins, spices, polyphenols, prebiotics and probiotics in the form of powders, tablets, capsules are currently marketed globally. Among them previous literatures have reported that polyphenols are the most promising compounds that have been proven to treat various chronic diseases like cancer, hypertension, diabetes mellitus (DM), osteoporosis, osteoarthritis, dyslipidemia, multiple sclerosis, congenital anomalies, Alzheimer’s disease, etc. It is warranted to discuss about the benefits of nanoformulations of nutraceuticals. Methods: We have searched PubMed using the keywords nutraceuticals, nanoformulations, therapeutic approaches, bionanotechnology, and therapeutics. The relevant papers and classical papers in this field were selected to write this review. Results and Discussion: The different classifications of nutraceuticals were elaborately described in this review. The comparison between the different categories of nutraceuticals with their nanoformulated forms was done explaining the benefits of nanoformulations regarding stability, bioavailability, enhanced antioxidant properties etc. A glimpse on the drawbacks of nanoformulations were also included. Conclusion: The current review highlights an overview of various nanoformulated nutraceuticals and its approach towards the treatment of multiple diseases.

scholarly journals The effect of metabolism on the course of labor and the postpartum period in highly productive cows

2020 ◽  
Vol 17 ◽  
pp. 00256
Author(s):  
Murat Baimishev ◽  
Sergey Eremin ◽  
Kirill Plemyashov ◽  
Hamidulla Baimishev ◽  
Igor Konopeltsev ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Postpartum Period ◽  
Early Stage ◽  
Antioxidant Properties ◽  
Antioxidant Systems ◽  
Dry Period ◽  
Blood Samples ◽  
Start Up ◽  
Significant Difference ◽  
Duration Of Pregnancy

The purpose of the research is to determine the etiopathogenesis of reproductive dysfunction in highly productive cows. For this, one group of cows was formed on the principle of paranalogs in the amount of 37 animals inseminated in the first sexual hunt after calving, followed by taking blood samples from them using the Monovet system, considering the duration of pregnancy. During the start-up period, blood was taken 1–4 days before calving and on the first day after calving. A total of 253 blood samples were examined. Subsequently, depending on the effectiveness of insemination, animals were divided into two groups. The first group included inseminated cows after the first insemination (20 animals), the second group included 17 unfertilized cows after the first insemination. Subsequently, blood was taken from animals considering the course of childbirth and the postpartum period. Blood counts were studied according to generally accepted methods using certified equipment. The study found that at an early stage of pregnancy, cows have a significant difference in lipid metabolism and in their peroxidation, in the state of antioxidant systems compared to unstable animals. In the process of pregnancy development in cows, there is a decrease in the level of total lipids and their class, and the accumulation of products of transoxidation of lipids is reduced. In animals with retention of the placenta, a low lipid metabolism and a higher level of peroxidation were established already in the dry period. After calving, this difference increases. The obtained data can be used to develop an algorithm for the prevention of postpartum complications in cows by using substances with antioxidant properties.

scholarly journals Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura K. Cole ◽  
Genevieve C. Sparagna ◽  
Marilyne Vandel ◽  
Bo Xiang ◽  
Vernon W. Dolinsky ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
Fatty Acid Uptake ◽  
Isoquinoline Alkaloid ◽  
Acid Uptake ◽  
High Fat ◽  
Low Fat

AbstractBerberine (BBR) is an isoquinoline alkaloid from plants known to improve cardiac mitochondrial function in gestational diabetes mellitus (GDM) offspring but the mechanism is poorly understood. We examined the role of the mitochondrial phospholipid cardiolipin (CL) in mediating this cardiac improvement. C57BL/6 female mice were fed either a Lean-inducing low-fat diet or a GDM-inducing high-fat diet for 6 weeks prior to breeding. Lean and GDM-exposed male offspring were randomly assigned a low-fat, high-fat, or high-fat diet containing BBR at weaning for 12 weeks. The content of CL was elevated in the heart of GDM offspring fed a high fat diet containing BBR. The increase in total cardiac CL was due to significant increases in the most abundant and functionally important CL species, tetralinoleoyl-CL and this correlated with an increase in the expression of the CL remodeling enzyme tafazzin. Additionally, BBR treatment increased expression of cardiac enzymes involved in fatty acid uptake and oxidation and electron transport chain subunits in high fat diet fed GDM offspring. Thus, dietary BBR protection from cardiac dysfunction in GDM exposed offspring involves improvement in mitochondrial function mediated through increased synthesis of CL.

scholarly journals C-Peptide as a Therapy for Type 1 Diabetes Mellitus

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 270
Author(s):  
Rachel L. Washburn ◽  
Karl Mueller ◽  
Gurvinder Kaur ◽  
Tanir Moreno ◽  
Naima Moustaid-Moussa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Complications ◽  
The United States ◽  
Genetically Engineered ◽  
Therapeutic Effects ◽  
Pancreatic Islet Transplantation ◽  
C Peptide ◽  
Increased Risk

Diabetes mellitus (DM) is a complex metabolic disease affecting one-third of the United States population. It is characterized by hyperglycemia, where the hormone insulin is either not produced sufficiently or where there is a resistance to insulin. Patients with Type 1 DM (T1DM), in which the insulin-producing beta cells are destroyed by autoimmune mechanisms, have a significantly increased risk of developing life-threatening cardiovascular complications, even when exogenous insulin is administered. In fact, due to various factors such as limited blood glucose measurements and timing of insulin administration, only 37% of T1DM adults achieve normoglycemia. Furthermore, T1DM patients do not produce C-peptide, a cleavage product from insulin processing. C-peptide has potential therapeutic effects in vitro and in vivo on many complications of T1DM, such as peripheral neuropathy, atherosclerosis, and inflammation. Thus, delivery of C-peptide in conjunction with insulin through a pump, pancreatic islet transplantation, or genetically engineered Sertoli cells (an immune privileged cell type) may ameliorate many of the cardiovascular and vascular complications afflicting T1DM patients.

scholarly journals Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 323
Author(s):  
Subrat Kumar Bhattamisra ◽  
Hui Min Koh ◽  
Shin Yean Lim ◽  
Hira Choudhury ◽  
Manisha Pandey
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Complications ◽  
Inflammatory Markers ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Neuroprotective Effect ◽  
Antioxidant Properties ◽  
Beneficial Effects ◽  
Ppar Γ ◽  
High Glucose Condition ◽  
Anti Inflammatory

Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords “Catalpol”, “Type 1 diabetes mellitus”, “Type 2 diabetes mellitus”, and “diabetic complications”. Catalpol promotes IRS-1/PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1α/PPAR-γ and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-κB and TGF-β/smad2/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-κB/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications.

scholarly journals Physical Activity and Redox Balance in the Elderly: Signal Transduction Mechanisms

2021 ◽  
Vol 11 (5) ◽  
pp. 2228
Author(s):  
Daniela Galli ◽  
Cecilia Carubbi ◽  
Elena Masselli ◽  
Mauro Vaccarezza ◽  
Valentina Presta ◽  
...  
Keyword(s):  
Physical Activity ◽  
Molecular Mechanisms ◽  
Vascular Tissue ◽  
The Elderly ◽  
Redox Balance ◽  
Antioxidant Systems ◽  
Targeted Prevention ◽  
Individual Subject ◽  
Aged People ◽  
The Individual

Reactive Oxygen Species (ROS) are molecules naturally produced by cells. If their levels are too high, the cellular antioxidant machinery intervenes to bring back their quantity to physiological conditions. Since aging often induces malfunctioning in this machinery, ROS are considered an effective cause of age-associated diseases. Exercise stimulates ROS production on one side, and the antioxidant systems on the other side. The effects of exercise on oxidative stress markers have been shown in blood, vascular tissue, brain, cardiac and skeletal muscle, both in young and aged people. However, the intensity and volume of exercise and the individual subject characteristics are important to envisage future strategies to adequately personalize the balance of the oxidant/antioxidant environment. Here, we reviewed the literature that deals with the effects of physical activity on redox balance in young and aged people, with insights into the molecular mechanisms involved. Although many molecular pathways are involved, we are still far from a comprehensive view of the mechanisms that stand behind the effects of physical activity during aging. Although we believe that future precision medicine will be able to transform exercise administration from wellness to targeted prevention, as yet we admit that the topic is still in its infancy.

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