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https://www.readbyqxmd.com/read/28874953/pleiotropic-effects-of-biguanides-on-mitochondrial-reactive-oxygen-species-production
#1
Alena Pecinova, Zdenek Drahota, Jana Kovalcikova, Nikola Kovarova, Petr Pecina, Lukas Alan, Michal Zima, Josef Houstek, Tomas Mracek
Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28815303/effect-of-barley-supplementation-on-the-fecal-microbiota-caecal-biochemistry-and-key-biomarkers-of-obesity-and-inflammation-in-obese-db-db-mice
#2
Jose F Garcia-Mazcorro, David A Mills, Kevin Murphy, Giuliana Noratto
PURPOSE: Barley is a low-glycemic index grain that can help diabetic and obese patients. The effect of barley intake depends on the host and the associated gut microbiota. This study investigated the effect of barley intake on the fecal microbiota, caecal biochemistry, and key biomarkers of obesity and inflammation. METHODS: Obese db/db mice were fed diets with and without barley during 8 weeks; lean mice were used as lean controls. Fecal microbiota was evaluated using 16S marker gene sequencing in a MiSeq instrument; several markers of caecal biochemistry, obesity, and inflammation were also evaluated using standard techniques...
August 16, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28814103/annals-express-associations-between-glycaemic-control-and-activation-of-the-renin-angiotensin-aldosterone-system-in-participants-with-type-2-diabetes-mellitus-and-hypertension
#3
Tomas Patrick Griffin, Deirdre Wall, Gerard A Browne, Michael C Dennedy, Paula O'Shea
INTRODUCTION: Hyperglycaemia increases succinate levels and succinate receptor (GPR91) activation in the kidney resulting in renin release. The aim of our study was to determine if there is an association between glycaemic control as evidenced by glycated haemoglobin (HbA1c) values and activation of the renin-angiotensin-aldosterone-system in patients with type 2 diabetes mellitus (T2DM) and hypertension. METHODS: A cross-sectional study was conducted at Galway University Hospitals between December 2014 and March 2015...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28813209/galangin-a-natural-flavonoid-reduces-mitochondrial-oxidative-damage-in-streptozotocin-induced-diabetic-rats
#4
Amal A Aloud, Chinnadurai Veeramani, Chandramohan Govindasamy, Mohammed A Alsaif, Khalid S Al-Numair
OBJECTIVE: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats. METHODS: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40 mg kg(-1) body weight (BW)). Galangin (8 mg kg(-1) BW) or glibenclamide (600 µg kg(-1) BW) was given orally daily once for 45 days to both healthy and diabetic rats. RESULTS: Diabetic rats showed significant (P < 0...
August 16, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28780379/proinflammatory-cytokine-mif-plays-a-role-in-the-pathogenesis-of-type-2-diabetes-mellitus-but-does-not-affect-hepatic-mitochondrial-function
#5
Miriam Rodriguez-Sosa, Tecilli Cabellos-Avelar, Yuriko Sanchez-Zamora, Imelda Juárez-Avelar, Esperanza García-Reyes, Alejandra Lira-León, José Del Carmen Benítez-Flores, Thalia Pacheco-Fernández, Marcia Hiriart, Emma Berta Gutiérrez-Cirlos
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Although the effect of high glucose on liver function has been described, the role of MIF in hepatic mitochondrial function during T2DM has not been studied. OBJECTIVE: We examine the influence of MIF to hepatic mitochondrial function in T2DM mouse model. METHODS: WT and Mif(-/-) BALB/c mice were treated with a single dose of streptozotocin (STZ)...
August 2, 2017: Cytokine
https://www.readbyqxmd.com/read/28763556/modifications-in-retinal-mitochondrial-respiration-precede-type-2-diabetes-and-protracted-microvascular-retinopathy
#6
Woo Hyun Han, Jonathan Gotzmann, Sharee Kuny, Hui Huang, Catherine B Chan, Hélène Lemieux, Yves Sauvé
Purpose: To characterize retinal mitochondrial respiration associated with type 2 diabetes (T2D) progression in a cone-rich diurnal rodent, the Nile rat (genus Arvicanthis, species niloticus). Methods: Nile rats were fed a standard rodent diet that resulted in rising glucose levels from 6 months. Age-matched control animals were fed a high-fiber diet that prevented diabetes up to 18 months. The functional status of specific retinal mitochondrial components and mitochondrial outer membrane integrity were studied by using high-resolution respirometry...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28738167/methylene-blue-improves-mitochondrial-respiration-and-decreases-oxidative-stress-in-a-substrate-dependent-manner-in-diabetic-rat-hearts
#7
Oana M Duicu, Andreea Privistirescu, Adrian Wolf, Alexandra Petrus, Maria D Dănilă, Corina Ratiu, Danina M Muntean, Adrian Sturza
Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox-drug with reported protective effects mainly on brain mitochondria. The present study was purported to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H2O2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats...
July 24, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28638031/-anxiolytic-and-antidepressant-effects-of-emoxipine-reamberin-and-mexidol-in-experimental-diabetes-mellitus
#8
I A Volchegorskii, I Yu Miroshnichenko, L M Rassokhina, R M Faizullin, K E Pryakhina
AIM: To perform a comparative study of anxiolytic and antidepressant effects of derivatives of 3-oxypyridine and succinic acid (emoxipine, reamberin and mexidol) in experimental diabetes mellitus. MATERIAL AND METHODS: An effect of emoxipine, reamberin and mexidol on manifestations of anxiety in 'elevated plus maze' (EPM) and duration of 'desperate behavior' (DB) in Porsolt test in rats with alloxan diabetes during medication course was studied. Alpha-lipoic (thioctic) acid (α-LA) was used as a reference drug...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28626178/hypoglycemic-coma-induced-by-the-use-of-succinic-acid-cibenzoline-in-frail-late-stage-elderly-subjects
#9
Yurie Hirata, Shinji Kamei, Fuminori Tatsumi, Masashi Shimoda, Akihito Tanabe, Junpei Sanada, Yoshiro Fushimi, Shintaro Irie, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
Succinic acid cibenzoline (CZ) is an antiarrhythmic agent often used for the treatment of tachyarrhythmia. However, hypoglycemia should be avoided in the treatment of diabetes. We herein report two late-stage elderly subjects who experienced a severe and prolonged hypoglycemic coma after the usage of CZ. These cases suggest that, when CZ is administered to elderly subjects with renal dysfunction and/or frailty, we should be aware of the possibility that this medicine may induce hypoglycemia and should adjust the dose as appropriate and monitor the concentration of CZ to avoid severe hypoglycemia...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28617536/effects-of-mulberry-leaf-polysaccharide-on-oxidative-stress-in-pancreatic-%C3%AE-cells-of-type-2-diabetic-rats
#10
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/28593900/phellinus-rimosus-improves-mitochondrial-energy-status-and-attenuates-nephrotoxicity-in-diabetic-rats
#11
K A Rony, T A Ajith, Tony A Kuttikadan, R Blaze, K K Janardhanan
BACKGROUND: Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. METHODS: Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation...
September 26, 2017: Journal of Basic and Clinical Physiology and Pharmacology
https://www.readbyqxmd.com/read/28561074/succinate-and-its-g-protein-coupled-receptor-stimulates-osteoclastogenesis
#12
Yuqi Guo, Chengzhi Xie, Xiyan Li, Jian Yang, Tao Yu, Ruohan Zhang, Tianqing Zhang, Deepak Saxena, Michael Snyder, Yingjie Wu, Xin Li
The mechanism underlying bone impairment in patients with diabetes mellitus, a metabolic disorder characterized by chronic hyperglycaemia and dysregulation in metabolism, is unclear. Here we show the difference in the metabolomics of bone marrow stromal cells (BMSCs) derived from hyperglycaemic (type 2 diabetes mellitus, T2D) and normoglycaemic mice. One hundred and forty-two metabolites are substantially regulated in BMSCs from T2D mice, with the tricarboxylic acid (TCA) cycle being one of the primary metabolic pathways impaired by hyperglycaemia...
May 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28539261/g-protein-coupled-receptor-91-signaling-in-diabetic-retinopathy-and-hypoxic-retinal-diseases
#13
Jianyan Hu, Tingting Li, Xinhua Du, Qiang Wu, Yun-Zheng Le
G protein-coupled receptor 91 (GPR91) is a succinate-specific receptor and activation of GPR91 could initiate a complex signal transduction cascade and upregulate inflammatory and pro-angiogenic cytokines. In the retina, GPR91 is predominately expressed in ganglion cells, a major cellular entity involved in the pathogenesis of diabetic retinopathy (DR) and other hypoxic retinal diseases. During the development of DR and retinopathy of prematurity (ROP), chronic hypoxia causes an increase in the levels of local succinate...
May 21, 2017: Vision Research
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#14
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE also occurs faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had accelerated GE...
August 2017: Gastroenterology
https://www.readbyqxmd.com/read/28382382/sucnr1-mediated-chemotaxis-of-macrophages-aggravates-obesity-induced-inflammation-and-diabetes
#15
Janna A van Diepen, Joris H Robben, Guido J Hooiveld, Claudia Carmone, Mohammad Alsady, Lily Boutens, Melissa Bekkenkamp-Grovenstein, Anneke Hijmans, Udo F H Engelke, Ron A Wevers, Mihai G Netea, Cees J Tack, Rinke Stienstra, Peter M T Deen
AIMS/HYPOTHESIS: Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by proinflammatory stimuli. We therefore investigated whether succinate receptor 1 (SUCNR1) could play a role in the development of adipose tissue inflammation and type 2 diabetes. METHODS: Succinate levels were determined in human plasma samples from individuals with type 2 diabetes and non-diabetic participants...
July 2017: Diabetologia
https://www.readbyqxmd.com/read/28376661/succination-of-protein-disulfide-isomerase-links-mitochondrial-stress-and-endoplasmic-reticulum-stress-in-the-adipocyte-during-diabetes
#16
Allison M Manuel, Michael D Walla, Adam Faccenda, Stephanie L Martin, Ross M Tanis, Gerardo G Piroli, Julie Adam, Boris Kantor, Bulent Mutus, Danyelle M Townsend, Norma Frizzell
AIMS: Protein succination by fumarate increases in the adipose tissue of diabetic mice and in adipocytes matured in high glucose as a result of glucotoxicity-driven mitochondrial stress. The endoplasmic reticulum (ER) oxidoreductase protein disulfide isomerase (PDI) is succinated in adipocytes that are matured in high glucose, and in this study we investigated whether succination would alter PDI oxidoreductase activity, directly linking mitochondrial stress and ER stress. RESULTS: Protein succination and the ER stress marker C/EBP homologous protein (CHOP) were diminished after pharmaceutical targeting of mitochondrial stress with the chemical uncoupler niclosamide in adipocytes matured in high-glucose concentrations...
May 19, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28280902/ginsenoside-rg5-attenuates-hepatic-glucagon-response-via-suppression-of-succinate-associated-hif-1%C3%AE-induction-in-hfd-fed-mice
#17
Na Xiao, Meng-Die Lou, Yi-Tong Lu, Le-Le Yang, Qun Liu, Baolin Liu, Lian-Wen Qi, Ping Li
AIMS/HYPOTHESIS: Ginsenosides regulate glucose homeostasis. This study investigated the effect of ginsenoside Rg5 (Rg5) on the hepatic glucagon response, focusing on the regulation of metabolism. METHODS: Mice fed a high-fat diet (HFD) showed increased hepatic glucose production (HGP). We observed the effects of Rg5 on hepatic fatty acid oxidation and glucagon response. The regulation of phosphodiesterase (PDE) 4B by succinate was also investigated in hepatocytes...
June 2017: Diabetologia
https://www.readbyqxmd.com/read/28253314/mangiferin-protects-against-adverse-skeletal-muscle-changes-and-enhances-muscle-oxidative-capacity-in-obese-rats
#18
Luz M Acevedo, Ana I Raya, Julio M Martínez-Moreno, Escolástico Aguilera-Tejero, José-Luis L Rivero
Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats...
2017: PloS One
https://www.readbyqxmd.com/read/28070703/nmr-based-metabolomics-reveals-brain-region-specific-metabolic-alterations-in-streptozotocin-induced-diabetic-rats-with-cognitive-dysfunction
#19
Hong Zheng, Qiuting Lin, Dan Wang, Pengtao Xu, Liangcai Zhao, Wenyi Hu, Guanghui Bai, Zhihan Yan, Hongchang Gao
Diabetes mellitus (DM) can result in cognitive dysfunction, but its potential metabolic mechanisms remain unclear. In the present study, we analyzed the metabolite profiling in eight different brain regions of the normal rats and the streptozotocin (STZ)-induced diabetic rats accompanied by cognitive dysfunction using a (1)H NMR-based metabolomic approach. A mixed linear model analysis was performed to assess the effects of DM, brain region and their interaction on metabolic changes. We found that different brain regions in rats displayed significant metabolic differences...
April 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28044282/are-prepubertal-children-metabolically-comparable-to-well-trained-adult-endurance-athletes
#20
REVIEW
Sébastien Ratel, Anthony J Blazevich
It is well acknowledged that prepubertal children have smaller body dimensions and a poorer mechanical (movement) efficiency, and thus a lower work capacity than adults. However, the scientific evidence indicates that prepubertal children have a greater net contribution of energy derived from aerobic metabolism in exercising muscle and reduced susceptibility to muscular fatigue, which makes them metabolically comparable to well-trained adult endurance athletes. For example, the relative energy contribution from oxidative and non-oxidative (i...
August 2017: Sports Medicine
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