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Mitochondrial diabetes

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https://www.readbyqxmd.com/read/28811861/importance-of-distinguishing-between-mitochondrial-encephalomyopathy-with-elderly-onset-of-stroke-like-episodes-and-cerebral-infarction
#1
Syuichi Tetsuka, Asako Tagawa, Tomoko Ogawa, Mieko Otsuka, Ritsuo Hashimoto, Hiroyuki Kato
The most common disease-causing mitochondrial DNA (mtDNA) mutation in mitochondrial encephalomyopathy (ME) with lactic acidosis and stroke-like episodes (MELAS) is m.3243A>G. In the future, the incidence of patients with cerebral infarction and diabetes mellitus is expected to increase tremendously. Additionally, the A3243G mutation typical of diabetes is estimated to be present in approximately 2% of all diabetes patients, which suggests that the potential disease population with a mitochondrial disorder is greater than previously thought, and there may have been many cases among the elderly that were misdiagnosed...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28811200/globular-adiponectin-reverses-osteo-sarcopenia-and-altered-body-composition-in-ovariectomized-rats
#2
Shyamsundar Pal China, Subhashis Pal, Sourav Chattopadhyay, Konica Porwal, Sapana Kushwaha, Sharmishtha Bhattacharyya, Monika Mittal, Anagha A Gurjar, Tarun Barbhuyan, Abhishek K Singh, Arun K Trivedi, Jiaur R Gayen, Sabyasachi Sanyal, Naibedya Chattopadhyay
Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied. Here, we studied the therapeutic effect of the globular form of adiponectin (gAd), which is predominantly an adipoR1 agonist, in aged ovariectomized (OVX) rats and compared it with standard-of-care anti-osteoporosis drugs...
August 12, 2017: Bone
https://www.readbyqxmd.com/read/28807765/sglt2-inhibitor-and-dpp-4-inhibitor-improve-brain-function-via-attenuating-mitochondrial-dysfunction-insulin-resistance-inflammation-and-apoptosis-in-hfd-induced-obese-rats
#3
Piangkwan Sa-Nguanmoo, Pongpan Tanajak, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn
Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks...
August 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803751/insulin-prevents-aberrant-mitochondrial-phenotype-in-sensory-neurons-of-type-1-diabetic-rats
#4
Mohamad-Reza Aghanoori, Darrell R Smith, Subir Roy Chowdhury, Mohammad Golam Sabbir, Nigel A Calcutt, Paul Fernyhough
Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochondrial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and expression of mitochondrial respiratory chain and insulin signaling-linked proteins...
August 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28801239/salsalate-activates-skeletal-muscle-thermogenesis-and-protects-mice-from-high-fat-diet-induced-metabolic-dysfunction
#5
Li Nie, Xin-Lu Yuan, Ke-Tao Jiang, Yu-Hui Jiang, Jin Yuan, Lan Luo, Shi-Wei Cui, Cheng Sun
Salsalate plays beneficial roles for ameliorating hyperglycemia and dyslipidemia in type 2 diabetes patients, but the underlying mechanisms are still poorly understood. In this study, by administering salsalate to mice fed with high fat diet and examining how salsalate rectifies metabolic dysfunction in these obese mice, we found that salsalate stimulated body temperature and attenuated body weight gain without affecting food intake. Our results showed that salsalate application decreased lipid accumulation in liver and epididymal white adipose tissue (eWAT), inhibited hepatic gluconeogenesis and improved insulin signaling transduction in eWAT...
August 4, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28800882/salvianolic-acid-b-inhibits-intermittent-high-glucose-induced-ins-1-cell-apoptosis-through-regulation-of-bcl-2-proteins-and-mitochondrial-membrane-potential
#6
Shanjun Tao, Younan Ren, Haowen Zheng, Mengqiu Zhao, Xu Zhang, Yuanmei Zhu, Jieren Yang, Shuguo Zheng
Blood glucose fluctuations, also referred to as intermittent high glucose, have been validated to be more harmful than sustained high glucose in exacerbating pancreatic dysfunction by inducing β cell apoptosis. Salvianolic acid B (Sal B), an aqueous component of Salvia miltiorrhiza, has been proved beneficial to pancreatic islet function in diabetes, but the underlying mechanisms remain to be elucidated. The present study investigated the protective effect of Sal B on INS-1 cells exposed to intermittent high glucose and the possible mechanisms implicated...
August 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28799503/understanding-the-role-and-mechanism-of-carbonic-anhydrase-v-in-obesity-and-its-therapeutic-implications
#7
Aarfa Queen, Parvez Khan, Amir Azam, Md Imtaiyaz Hassan
Obesity is a metabolic syndrome leading to several health problems such as hypertension, heart attack, type II diabetes, and even cancer. Carbonic anhydrase VA (CAVA) is a mitochondrial enzyme which is directly associated with the glucose homeostasis and considered as a promising target for obesity and other associated diseases in humans. So far, numerous inhibitors have been designed to inhibit the catalytic activity of CAVA with an assumption for its possible therapeutic uses against type II diabetes and other metabolic diseases...
August 10, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28798389/the-mitochondrial-derived-peptides-humanins14g-and-small-humanin-like-peptide-2-exhibit-chaperone-like-activity
#8
Alan K Okada, Kazuki Teranishi, Fleur Lobo, J Mario Isas, Jialin Xiao, Kelvin Yen, Pinchas Cohen, Ralf Langen
Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell's unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28793853/equine-skeletal-muscle-adaptations-to-exercise-and-training-evidence-of-differential-regulation-of-autophagosomal-and-mitochondrial-components
#9
Kenneth Bryan, Beatrice A McGivney, Gabriella Farries, Paul A McGettigan, Charlotte L McGivney, Katie F Gough, David E MacHugh, Lisa M Katz, Emmeline W Hill
BACKGROUND: A single bout of exercise induces changes in gene expression in skeletal muscle. Regular exercise results in an adaptive response involving changes in muscle architecture and biochemistry, and is an effective way to manage and prevent common human diseases such as obesity, cardiovascular disorders and type II diabetes. However, the biomolecular mechanisms underlying such responses still need to be fully elucidated. Here we performed a transcriptome-wide analysis of skeletal muscle tissue in a large cohort of untrained Thoroughbred horses (n = 51) before and after a bout of high-intensity exercise and again after an extended period of training...
August 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28792007/shared-molecular-and-cellular-mechanisms-of-premature-ageing-and-ageing-associated-diseases
#10
REVIEW
Nard Kubben, Tom Misteli
Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity...
August 9, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28790027/increased-mitochondrial-calcium-uniporter-in-adipocytes-underlies-mitochondrial-alterations-associated-with-insulin-resistance
#11
Lauren E Wright, Denis Vecellio Reane, Gabriella Milan, Anna Terrin, Giorgia di Bello, Anna Belligoli, Marta Sanna, Mirto Foletto, Francesca Favaretto, Anna Raffaello, Cristina Mammucari, Donato Nitti, Roberto Vettor, Rosario Rizzuto
Intracellular calcium influences an array of pathways and affects cellular processes. With the rapidly progressing research investigating the molecular identity and the physiological roles of the Mitochondrial Calcium Uniporter (MCU) complex, we now have the tools to understand the functions of mitochondrial Ca(2+) in the regulation of pathophysiological processes. Herein, we describe the role of key MCU complex components in insulin resistance in mouse and human adipose tissue. Adipose tissue gene expression was analysed from several models of obese and diabetic rodents and in obese patients, as well as in vitro insulin-resistant adipocytes...
August 8, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28781146/the-impact-of-foxo-1-to-cardiac-pathology-in-diabetes-mellitus-and-diabetes-related-metabolic-abnormalities
#12
Dimitry A Chistiakov, Alexander N Orekhov, Yuri V Bobryshev
Diabetic heart pathology has a serious social impact due to high prevalence worldwide and significant mortality/invalidation of diabetic patients suffered from cardiomyopathy. The pathogenesis of diabetic and diabetes-related cardiomyopathy is associated with progressive loss and impairment of cardiac function due to adverse effects of metabolic, prooxidant, proinflammatory, and pro-apoptotic stress factors. In the adult heart, the transcriptional factor forkhead box-1 (FOXO-1) is involved in maintaining cardiomyocytes in the homeostatic state and induction of their adaptation to metabolic and pro-oxidant stress stimuli...
August 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28780747/niclosamide-piperazine-prevents-high-fat-diet-induced-obesity-and-diabetic-symptoms-in-mice
#13
Jingjing Guo, Hanlin Tao, Amer Alasadi, Qingrong Huang, Shengkan Jin
PURPOSE: Obesity and type 2 diabetes (T2D) have become the major public health challenges globally. Mitochondrial uncoupling, which reduces intracellular lipid loads and corrects the underlying cause of insulin resistance, has emerged as a promising anti-obese and anti-diabetic intervention. Niclosamide is an anthelmintic drug approved by the US FDA with the mechanism of action that uncouples mitochondria of parasitic worms. Recently, niclosamide ethanolamine salt (NEN) was found to be a safe and effective hepatic mitochondrial uncoupler for the prevention and treatment of obesity and T2D in mouse models...
August 5, 2017: Eating and Weight Disorders: EWD
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
#14
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/28777009/importance-of-mitochondrial-calcium-uniporter-in-high-glucose-induced-endothelial-cell-dysfunction
#15
Wei Chen, Jie Yang, Shuhua Chen, Hong Xiang, Hengdao Liu, Dan Lin, Shaoli Zhao, Hui Peng, Pan Chen, Alex F Chen, Hongwei Lu
OBJECTIVE: Mitochondrial Ca(2+) overload is implicated in hyperglycaemia-induced endothelial cell dysfunction, but the key molecular events responsible remain unclear. We examined the involvement of mitochondrial calcium uniporter, which mediates mitochondrial Ca(2+) uptake, in endothelial cell dysfunction resulting from high-glucose treatment. METHODS: Human umbilical vein endothelial cells were exposed to various glucose concentrations and to high glucose (30 mM) following mitochondrial calcium uniporter inhibition or activation with ruthenium red and spermine, respectively...
August 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28776376/new-evidence-for-the-mechanism-of-action-of-a-type-2-diabetes-drug-using-a-magnetic-bead-based-automated-biosensing-platform
#16
Rokon Uddin, Nur E Habiba, Graham Rena, En Te Hwu, Anja Boisen
The mechanism of action (MOA) of the first line type-2 diabetes drug metformin remains unclear despite its widespread usage. However, recent evidence suggests that the mitochondrial copper (Cu)-binding action of metformin may contribute towards the drug's MOA. Here, we present a novel biosensing platform for investigating the MOA of metformin using a magnetic microbead -based agglutination assay which has allowed us to demonstrate for the first time the interaction between Cu and metformin at clinically relevant low micromolar concentrations of the drug, thus suggesting a potential pathway of metformin's blood-glucose lowering action...
August 4, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28776185/modulation-of-cellular-energetics-by-galactose-and-pioglitazone
#17
David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E Konkle, Nilay Chakraborty, Michael A Menze
The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences may occur in addition to sensitizing the cells to mitochondrial toxins. The screening of pharmaceutical agents against transformed cells while using galactose must therefore be carefully evaluated. Pioglitazone is employed in clinical applications to treat type-2 diabetes but clearly has other off-target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactose-containing medium to investigate the role of pioglitazone on cellular bioenergetics by calorimetry and respirometry...
August 3, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28776086/the-mechanisms-of-action-of-metformin
#18
REVIEW
Graham Rena, D Grahame Hardie, Ewan R Pearson
Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28772214/epigallocatechin-3-gallate-protects-against-diabetic-cardiomyopathy-through-modulating-the-cardiometabolic-risk-factors-oxidative-stress-inflammation-cell-death-and-fibrosis-in-streptozotocin-nicotinamide-induced-diabetic-rats
#19
Azza I Othman, Mamdouh R El-Sawi, Mohamed A El-Missiry, Mohammad H Abukhalil
The potential protective effect of epigallocatechin-3-gallate (EGCG) on type 2 diabetes-induced heart injury was investigated. A rat model of diabetes was achieved by injection of nicotinamide (100mg/kg, i.p), 20min before the administration of streptozotocin (55mg/kg, i.p.). After confirmation of diabetes, EGCG (2mg/kg, p.o.) was administrated on alternate days for one month. Treatment of diabetic rats with EGCG showed a remarkable reduction in glucose, glycosylated hemoglobin, HOMA-IR and lipid profile levels with an elevation in insulin levels, indicating its antihyperglycemic and antidyslipidemic actions...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28771714/multifunctional-curcumin-mediate-multitherapeutic-effects
#20
Adeeb Shehzad, Munibah Qureshi, Muhammad Nabeel Anwar, Young Sup Lee
Inflammation can promote the development of arthritis, obesity, cardiovascular, type II diabetes, pancreatitis, metabolic and neurodegenerative diseases, and certain types of cancer. Compounds isolated from plants have been practiced since ancient times for curing various ailments including inflammatory disorders and to support normal physiological functions. Curcumin (diferuloylmethane) is a yellow coloring agent, extracted from turmeric that has been used for the prevention and treatment of various inflammatory diseases...
August 3, 2017: Journal of Food Science
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