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Mitochondrial diabetes

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https://www.readbyqxmd.com/read/28095372/impaired-mitochondrial-respiration-in-large-cerebral-arteries-of-rats-with-type-2-diabetes
#1
Ivan Merdzo, Ibolya Rutkai, Venkata N L R Sure, Catherine A McNulty, Prasad V G Katakam, David W Busija
Mitochondrial dysfunction has been suggested as a potential underlying cause of pathological conditions associated with type 2 diabetes (T2DM). We have previously shown that mitochondrial respiration and mitochondrial protein levels were similar in the large cerebral arteries of insulin-resistant Zucker obese rats and their lean controls. In this study, we extend our investigations into the mitochondrial dynamics of the cerebral vasculature of 14-week-old Zucker diabetic fatty obese (ZDFO) rats with early T2DM...
January 18, 2017: Journal of Vascular Research
https://www.readbyqxmd.com/read/28094765/selective-antagonism-of-muscarinic-receptors-is-neuroprotective-in-peripheral-neuropathy
#2
Nigel A Calcutt, Darrell R Smith, Katie Frizzi, Mohammad Golam Sabbir, Subir K Roy Chowdhury, Teresa Mixcoatl-Zecuatl, Ali Saleh, Nabeel Muttalib, Randy Van der Ploeg, Joseline Ochoa, Allison Gopaul, Lori Tessler, Jürgen Wess, Corinne G Jolivalt, Paul Fernyhough
Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor-dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity...
January 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28091829/inhibition-of-dpp-4-activity-and-neuronal-atrophy-with-genistein-attenuates-neurological-deficits-induced-by-transient-global-cerebral-ischemia-and-reperfusion-in-streptozotocin-induced-diabetic-mice
#3
Mithun Singh Rajput, Purnima Dey Sarkar, Nilesh Prakash Nirmal
Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury...
January 16, 2017: Inflammation
https://www.readbyqxmd.com/read/28089584/pterostilbene-attenuates-high-glucose-induced-oxidative-injury-in-hippocampal-neuronal-cells-by-activating-nuclear-factor-erythroid-2-related-factor-2
#4
Yang Yang, Chongxi Fan, Bodong Wang, Zhiqiang Ma, Dongjin Wang, Bing Gong, Shouyin Di, Shuai Jiang, Yue Li, Tian Li, Zhi Yang, Erping Luo
In the present study, neuroblastoma (SH-SY5Y) cells were used to investigate the mechanisms mediating the potential protective effects of pterostilbene (PTE) against mitochondrial metabolic impairment and oxidative stress induced by hyperglycemia for mimicking the diabetic encephalopathy. High glucose medium (100 mM) decreased cellular viability after 24 h incubation which was evidenced by: (i) reduced mitochondrial complex I and III activities; (ii) reduced mitochondrial cytochrome C; (iii) increased reactive oxygen species (ROS) generation; (iv) decreased mitochondrial membrane potential (ΔΨm); and (v) increased lactate dehydrogenase (LDH) levels...
January 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088628/methods-needed-to-measure-predictive-accuracy-a-study-of-diabetic-patients
#5
Hafiz M R Khan, Sarah Mende, Aamrin Rafiq, Kemesha Gabbidon, P Hemachandra Reddy
Diabetes is one of the leading causes of morbidity and mortality and it can result in several complications such as kidney failure, heart failure, stroke, and blindness making it a major medical and public health concern in the United States. Statistical methods are important to detect risk factors and identify the best sampling plan to determine predictive bounds for diabetic patients' data. The main objective of this paper is to identify the best fit bootstrapping sampling method and to draw the predictive bound considering diabetes patient data...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#6
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28087670/plant-lectins-activate-the-nlrp3-inflammasome-to-promote-inflammatory-disorders
#7
Tao Gong, Xiaqiong Wang, Yanqing Yang, Yiqing Yan, Chenggong Yu, Rongbin Zhou, Wei Jiang
Plant-derived dietary lectins have been reported to be involved in the pathogenesis of several inflammatory diseases, including inflammatory bowel disease, diabetes, rheumatoid arthritis, and celiac disease, but little is known about the molecular mechanisms underlying lectin-induced inflammation. In this study, we showed that plant lectins can induce caspase-1 activation and IL-1β secretion via the NLRP3 inflammasome. Lectins were internalized and subsequently escaped from the lysosome and then translocated to the endoplasmic reticulum...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28079150/sustained-kidney-biochemical-derangement-in-treated-experimental-diabetes-a-clue-to-metabolic-memory
#8
Antonio Anax F de Oliveira, Tiago F de Oliveira, Larissa L Bobadilla, Camila C M Garcia, Carolina Maria Berra, Nadja C de Souza-Pinto, Marisa H G Medeiros, Paolo Di Mascio, Roberto Zatz, Ana Paula de M Loureiro
The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077274/the-role-and-regulation-of-the-peroxisome-proliferator-activated-receptor-alpha-in-human-liver
#9
REVIEW
Sander Kersten, Rinke Stienstra
The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that is abundantly expressed in liver. PPARα is activated by fatty acids and various other lipid species, as well as by a class of chemicals referred to as peroxisome proliferators. Studies in mice have shown that PPARα serves as the master regulator of hepatic lipid metabolism during fasting. In addition, PPARα suppresses inflammation and the acute phase response. Comparatively little is known about PPARα in human liver...
January 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28074262/activated-microglia-induce-the-production-of-reactive-oxygen-species-and-promote-apoptosis-of-co-cultured-retinal-microvascular-pericytes
#10
Xinyi Ding, Meng Zhang, Ruiping Gu, Gezhi Xu, Haixiang Wu
PURPOSE: Pericyte apoptosis is a predominant feature of early diabetic retinopathy. In diabetic retinopathy, activated microglia migrate and release proinflammatory cytokines that contribute to disruption of the blood-retinal barrier, neuronal loss, and enhanced ROS production. Reactive oxygen species (ROS) are implicated in pericyte death; however, the mechanism by which activated microglia affect retinal microvascular pericytes is unclear. We hypothesized that activated microglia may promote pericyte apoptosis by enhancing ROS production...
January 10, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28073829/dutpase-dut-is-mutated-in-a-novel-monogenic-syndrome-with-diabetes-and-bone-marrow-failure
#11
Reinaldo Sousa Dos Santos, Mathilde Daures, Anne Philippi, Sophie Romero, Lorella Marselli, Piero Marchetti, Valérie Senée, Delphine Bacq, Céline Besse, Baz Baz, Laura Marroquí, Sarah Ivanoff, Julien Masliah-Planchon, Marc Nicolino, Jean Soulier, Gérard Socié, Decio L Eizirik, Jean-François Gautier, Cécile Julier
We describe a new syndrome characterized by early onset diabetes mellitus, associated with bone marrow failure affecting mostly the erythrocytic lineage. Using whole exome sequencing in a remotely consanguineous patient from a family with two affected siblings, we identified a single homozygous missense mutation (chr15.hg19:g.48,626,619A>G) located in the dUTPase (DUT) gene (NCBI Gene ID: 1854), affecting both the mitochondrial (DUT-M p.Y142C) and the nuclear (DUT-N p.Y54C) isoforms. We found the same homozygous mutation in an unrelated consanguineous patient with diabetes and bone marrow aplasia from a family with two affected siblings, while none of the >60,000 subjects from the Exome Aggregation Consortium (ExAC) was homozygous for this mutation...
January 10, 2017: Diabetes
https://www.readbyqxmd.com/read/28073120/nano-pelargonidin-protects-hyperglycemic-induced-l6-cells-against-mitochondrial-dysfunction
#12
Asmita Samadder, Debojyoti Tarafdar, Suresh K Abraham, Kumaresh Ghosh, Anisur Rahman Khuda-Bukhsh
Nano-encapsulation of several natural products has become an important tool in enhancing the bioavailability of some modern drugs against many diseases. Pelargonidin is an anthocyanidin found in many fruits and vegetables. Pelargonidin is loaded with poly-lactide-co-glycolic-acid, a non-toxic biodegradable polymer, to produce nano-pelargonidin. Size, morphology, zeta potential, and planar uniformity of formulated nano-pelargonidin were determined by atomic force microscopy and dynamic light scattering. The time required for cellular entry, folds of nano-pelargonidin, and drug encapsulation efficiency of poly-lactide-co-glycolic-acid were also ascertained...
January 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28072841/a-small-insulinomimetic-molecule-also-improves-insulin-sensitivity-in-diabetic-mice
#13
Sandip Mukherjee, Mrittika Chattopadhyay, Sushmita Bhattacharya, Suman Dasgupta, Sahid Hussain, Saitanya K Bharadwaj, Dhrubajyoti Talukdar, Abul Usmani, Bhola S Pradhan, Subeer S Majumdar, Pronobesh Chattopadhyay, Satinath Mukhopadhyay, Tushar K Maity, Mihir K Chaudhuri, Samir Bhattacharya
Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1...
2017: PloS One
https://www.readbyqxmd.com/read/28069865/interleukin-22-restored-mitochondrial-damage-and-impaired-glucose-stimulated-insulin-secretion-through-down-regulation-of-uncoupling-protein-2-in-ins-1-cells
#14
Minling Hu, Hanxiao Lin, Li Yang, Yanzhen Cheng, Hua Zhang
Defective glucose-stimulated insulin secretion (GSIS) induced by chronic exposure to fatty acids is a hallmark of type 2 diabetes (T2D). Interleukin-22 (IL-22) has been shown to exert beneficial effects on insulin secretion and to protect pancreatic β-cells from stress. Moreover, uncoupling protein-2 (UCP-2) plays a central role in the regulation of GSIS and β-cell dysfunction, whereas the role of UCP-2 in IL-22-enhanced glycemic control under conditions of lipotoxicity remains unclear. In this present study, we investigated the effects of IL-22 on rat insulin-secreting cells (INS-1 cells) and the mechanisms that underlie IL-22 and lipotoxicity-impaired GSIS in vitro...
January 7, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28069019/ppars-modulate-cardiac-metabolism-and-mitochondrial-function-in-diabetes
#15
REVIEW
Ting-Wei Lee, Kuan-Jen Bai, Ting-I Lee, Tze-Fan Chao, Yu-Hsun Kao, Yi-Jen Chen
Diabetic cardiomyopathy is a major complication of diabetes mellitus (DM). Currently, effective treatments for diabetic cardiomyopathy are limited. The pathophysiology of diabetic cardiomyopathy is complex, whereas mitochondrial dysfunction plays a vital role in the genesis of diabetic cardiomyopathy. Metabolic regulation targeting mitochondrial dysfunction is expected to be a reasonable strategy for treating diabetic cardiomyopathy. Peroxisome proliferator-activated receptors (PPARs) are master executors in regulating glucose and lipid homeostasis and also modulate mitochondrial function...
January 10, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28067471/traditional-and-novel-tools-to-probe-the-mitochondrial-metabolism-in-health-and-disease
#16
REVIEW
Yanfei Zhang, José L Avalos
Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer...
January 9, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28064117/differential-proteomic-and-oxidative-profiles-unveil-dysfunctional-protein-import-to-adipocyte-mitochondria-in-obesity-associated-aging-and-diabetes
#17
María Gómez-Serrano, Emilio Camafeita, Juan A López, Miguel A Rubio, Irene Bretón, Inés García-Consuegra, Eva García-Santos, Jesús Lago, Andrés Sánchez-Pernaute, Antonio Torres, Jesús Vázquez, Belén Peral
Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28062795/silac-based-proteomics-of-primary-human-kidney-cells-reveals-a-novel-link-between-male-sex-hormones-and-impaired-energy-metabolism-in-diabetic-kidney-disease
#18
Sergi Clotet, Maria Jose Soler, Marta Riera, Julio Pascual, Fei Fang, Joyce Zhou, Ihor Batruch, Stella K Vasiliou, Apostolos Dimitromanolakis, Clara Barrios, Eleftherios Diamandis, James Scholey, Ana Konvalinka
Male sex predisposes to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within kidney, we hypothesized that dihydrotestosterone (DHT) would alter the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT- and 17β-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC). Of the 5043 quantified proteins, 76 were differentially regulated...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28061969/role-of-nitric-oxide-in-stress-induced-anxiety-from-pathophysiology-to-therapeutic-target
#19
A Kumar, P Chanana
Stress is often marked by a state of hyperarousal to aid the initiation of necessary stress response for the successful management of stressful stimuli. It can be manifested as a challenge (stimulus) that requires behavioral, psychological, and physiological adaptations for the maintenance of a state of homeostasis in response to stressful stimuli. In an organism, miscellaneous stressors trigger a wide spectrum of alterations in hormonal and neuronal physiologies, resulting in behavioral (anxiety and depression disorders, diminished food intake and gastrointestinal dysfunctions, decline in sexual behavior, diabetes, and loss of cognitive function) and other physiological responses...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28059465/rosmarinic-acid-mediates-mitochondrial-biogenesis-in-insulin-resistant-skeletal-muscle-through-activation-of-ampk
#20
Govindaraj Jayanthy, Vellai Roshana Devi, Kaliappan Ilango, Sorimuthu Pillai Subramanian
Rosmarinic acid (RA), a polyphenol, is known to improve hepatic insulin sensitivity in experimental type 2 diabetes. However, its effect on skeletal muscle insulin resistance is meagerly understood. The present study was aimed to investigate the upstream and downstream mediators of the molecular targets of RA in attenuating insulin resistance in the skeletal muscle both in vivo and in vitro. We found that supplementation of RA increased the expression of key genes involved in the mitochondrial biogenesis like PGC-1α, SIRT-1 and TFAM via activation of AMPK in the skeletal muscle of insulin resistant rats as well as in L6 myotubes...
January 6, 2017: Journal of Cellular Biochemistry
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