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Mitochondrial diabetes

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https://www.readbyqxmd.com/read/28644886/complex-i-inhibition-augments-dichloroacetate-cytotoxicity-through-enhancing-oxidative-stress-in-vm-m3-glioblastoma-cells
#1
Nathan P Ward, Angela M Poff, Andrew P Koutnik, Dominic P D'Agostino
The robust glycolytic metabolism of glioblastoma multiforme (GBM) has proven them susceptible to increases in oxidative metabolism induced by the pyruvate mimetic dichloroacetate (DCA). Recent reports demonstrate that the anti-diabetic drug metformin enhances the damaging oxidative stress associated with DCA treatment in cancer cells. We sought to elucidate the role of metformin's reported activity as a mitochondrial complex I inhibitor in the enhancement of DCA cytotoxicity in VM-M3 GBM cells. Metformin potentiated DCA-induced superoxide production, which was required for enhanced cytotoxicity towards VM-M3 cells observed with the combination...
2017: PloS One
https://www.readbyqxmd.com/read/28642704/quercetin-a-lead-compound-against-type-2-diabetes-ameliorates-glucose-uptake-via-ampk-pathway-in-skeletal-muscle-cell-line
#2
R Dhanya, A D Arya, P Nisha, P Jayamurthy
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28641785/acute-detachment-of-hexokinase-ii-from-mitochondria-modestly-increases-oxygen-consumption-of-the-intact-mouse-heart
#3
Rianne Nederlof, Simone Denis, Benjamin Lauzier, Christine Des Rosiers, Markku Laakso, Jacob Hagen, Carmen Argmann, Ronald Wanders, Riekelt H Houtkooper, Markus W Hollmann, Sander M Houten, Coert J Zuurbier
OBJECTIVE: Cardiac hexokinase II (HKII) can translocate between cytosol and mitochondria and change its cellular expression with pathologies such as ischemia-reperfusion, diabetes and heart failure. The cardiac metabolic consequences of these changes are unknown. Here we measured energy substrate utilization in cytosol and mitochondria using stabile isotopes and oxygen consumption of the intact perfused heart for 1) an acute decrease in mitochondrial HKII (mtHKII), and 2) a chronic decrease in total cellular HKII...
July 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#4
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28640453/corrigendum
#5
(no author information available yet)
Diabetic cardiomyopathy (DCM) was first recognized more than four decades ago and occurred independent of cardiovascular diseases or hypertension in both type 1 and type 2 diabetic patients. The exact mechanisms underlying this disease remain incompletely understood. Several pathophysiological bases responsible for DCM have been proposed, including the presence of hyperglycemia, nonenzymatic glycosylation of large molecules (e.g., proteins), energy metabolic disturbance, mitochondrial damage and dysfunction, impaired calcium handling, reactive oxygen species formation, inflammation, cardiac cell death, and cardiac hypertrophy and fibrosis, leading to impairment of cardiac contractile functions...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28639457/glyoxal-toxicity-in-isolated-rat-liver-mitochondria
#6
M Goudarzi, H Kalantari, M Rezaei
Glyoxal is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose, and degradation of glycated proteins. Glyoxal has been linked to oxidative stress and can cause a number of cellular damages, including covalent modification of amino and thiol groups of proteins to form advanced glycation end products. However, the mechanism of glyoxal toxicity has not been fully understood. In this study, we have focused on glyoxal toxicity in isolated rat liver mitochondria...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28636532/a-novel-pan-nox-inhibitor-apx-115-protects-kidney-injury-in-streptozotocin-induced-diabetic-mice-possible-role-of-peroxisomal-and-mitochondrial-biogenesis
#7
Guideock Kwon, Md Jamal Uddin, Gayoung Lee, Songling Jiang, Ahreum Cho, Jung Hwa Lee, Sae Rom Lee, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae Ryong Cha, Hunjoo Ha
NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are increasingly recognized as a key factor in inflammation and extracellular matrix accumulation in diabetic kidney disease. APX-115 (3-phenyl-1-(pyridin-2-yl)-4-propyl-1-5-hydroxypyrazol HCl) is a novel orally active pan-Nox inhibitor. The objective of this study was to compare the protective effect of APX-115 with a renin-angiotensin system inhibitor (losartan), the standard treatment against kidney injury in diabetic patients, on streptozotocin (STZ)-induced diabetic kidney injury...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-non-alcoholic-steatohepatitis-and-liver-fibrosis
#8
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis and increased cardiovascular mortality. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are indirect glucagon like peptide 1 (GLP-1) agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
June 21, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#9
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28630460/oxidative-and-endoplasmic-reticulum-stress-is-impaired-in-leukocytes-from-metabolically-unhealthy-vs-healthy-obese-individuals
#10
C Bañuls, S Rovira-Llopis, S Lopez-Domenech, N Diaz-Morales, A Blas-Garcia, S Veses, C Morillas, V M Victor, M Rocha, A Hernandez-Mijares
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)...
June 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28627583/deoxyactein-protects-pancreatic-%C3%AE-cells-against-methylglyoxal-induced-oxidative-cell-damage-by-the-upregulation-of-mitochondrial-biogenesis
#11
Kwang Sik Suh, Eun Mi Choi, Woon-Won Jung, Yu Jin Kim, Soo Min Hong, So Yong Park, Sang Youl Rhee, Suk Chon
Methylglyoxal (MG) is one of the major precursors of advanced glycation end products (AGEs), which are considered to be one of the causes of diabetes and its complications. The root and rhizomes of black cohosh (Cimicifuga racemosa) have long been used medicinally, and deoxyactein is one of its major constituents. In the present study, the protective effects of deoxyactein against MG-induced oxidative cell damage were investigated in insulin-producing pancreatic β-cells. We found that deoxyactein protected the pancreatic β-cells against MG-induced cell death...
June 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28625088/mitochondrial-content-and-hepcidin-are-increased-in-obese-pregnant-mothers
#12
G M Anelli, M Cardellicchio, C Novielli, P Antonazzo, M I Mazzocco, I Cetin, C Mandò
OBJECTIVE: Maternal obesity is characterized by systemic low-grade inflammation and oxidative stress (OxS) with the contribution of fetal sex dimorphism. We recently described increased mitochondrial content (mtDNA) in placentas of obese pregnancies. Here we quantify mtDNA and hepcidin as indexes of OxS and systemic inflammation in the obese maternal circulation. METHODS: Forty-one pregnant women were enrolled at elective Caesarean section: 16 were normal-weight [NW] and 25 were obese (OB)...
June 18, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28624657/adiponectin-improves-the-osteointegration-of-titanium-implant-under-diabetic-conditions-by-reversing-mitochondrial-dysfunction-via-the-ampk-pathway-in-vivo-and-in-vitro
#13
Xiao-Fan Hu, Lin Wang, Yi-Zhao Lu, Geng Xiang, Zi-Xiang Wu, Ya-Bo Yan, Yang Zhang, Xiong Zhao, Yuan Zang, Lei Shi, Wei Lei, Ya-Fei Feng
Diabetes-induced reactive oxygen species (ROS) overproduction would result in compromised osteointegration of titanium implant (TI) and high rate of implant failure, yet the underlying mechanisms remain elusive. Adiponectin (APN) is a fat-derived adipocytokine with strong antioxidant, mitochondrial-protective and anti-diabetic efficacies. We hypothesized that mitochondrial dysfunction under diabetes may account for the oxidative stress in osteoblasts and titanium-bone interface (TBI) instability, which could be ameliorated by APN...
June 14, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28624654/insulin-signaling-an-opportunistic-target-to-minify-risk-of-alzheimer-s-disease
#14
REVIEW
Rohit Pardeshi, Nityanand Bolshette, Kundlik Gadhave, Ashutosh Ahire, Sahabuddin Ahmed, Tommaso Cassano, Veer Bala Gupta, Mangala Lahkar
Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by accumulation of senile plaques, neurofibrillary tangles (NFT) and neurodegeneration. The diabetes mellitus (DM) is one of the risk factors for AD pathogenesis by impairment in insulin signaling and glucose metabolism in central as well as peripheral system. Insulin resistance, impaired glucose and lipid metabolism lead to the Aβ (Aβ) aggregation, Tau phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, memory impairment and also mark over Aβ transport through central to peripheral and vice versa...
May 30, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28620552/refractory-lactic-acidosis-in-small-cell-carcinoma-of-the-lung
#15
Daniel J Oh, Ellen Dinerman, Andrew H Matthews, Abraham W Aron, Katherine M Berg
BACKGROUND: Elevated lactate levels in critically ill patients are most often thought to be indicative of relative tissue hypoxia or type A lactic acidosis. Shock, severe anemia, and thromboembolic events can all cause elevated lactate due to tissue hypoperfusion, as well as the mitochondrial dysfunction thought to occur in sepsis and other critically ill states. Malignancy can also lead to elevation in lactate, a phenomenon described as type B lactic acidosis, which is much less commonly encountered in the critically ill...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#16
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28617536/effects-of-mulberry-leaf-polysaccharide-on-oxidative-stress-in-pancreatic-%C3%AE-cells-of-type-2-diabetic-rats
#17
C-G Liu, Y-P Ma, X-J Zhang
OBJECTIVE: To explore and discuss the effects and mechanisms of mulberry leaf polysaccharide (MLP) on oxidative stress in pancreatic β-cells of type 2 diabetic rats. MATERIALS AND METHODS: The model of diabetic rats was established by inducing the Sprague-Dawley (SD) rats with high-sugar and high-fat diet for 6 weeks and then giving them streptozotocin (STZ) by single intraperitoneal injection. The mulberry leaf polysaccharide was administered via gavage daily for 8 weeks, and the tissue morphology was observed through electron microscopy...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#18
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, Chi Hu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608965/hydrogen-sulphide-modulating-mitochondrial-morphology-to-promote-mitophagy-in-endothelial-cells-under-high-glucose-and-high-palmitate
#19
Ning Liu, Jichao Wu, Linxue Zhang, Zhaopeng Gao, Yu Sun, Miao Yu, Yajun Zhao, Shiyun Dong, Fanghao Lu, Weihua Zhang
Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 μM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 μM NaHS was used as an exogenous H2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H2 S production and CSE expression in RAECs...
June 13, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28608258/extracts-of-chrysanthemum-zawadskii-attenuate-oxidative-damage-to-vascular-endothelial-cells-caused-by-a-highly-reducing-sugar
#20
Hyun-Sook Kim
Endothelial cells are considered candidates for involvement in the pathogenesis of diabetic vascular complications, and prevention of endothelial cell damage may be important in pharmacological attempts to prevent such complications. In the present study, I explored whether extracts of Chrysanthemum zawadskii (CZE) could prevent oxidative damage and dysfunction of a vascular endothelial cell line caused by the highly reducing sugar, 2-deoxy-D-ribose (dRib), and dysfunction of a vascular endothelial cell line...
June 12, 2017: Cytotechnology
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