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Mitochondrial diabetes

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https://www.readbyqxmd.com/read/28444922/regulation-of-organelle-function-by-metformin
#1
REVIEW
Jeongho Kim, Young-Jai You
Metformin ameliorates hyperglycemia without the side effects of lactic acidosis or hypoglycemia. Metformin lowers the blood glucose level by decreasing hepatic glucose production in the liver and by increasing glucose uptake in the muscle. Recent studies show that metformin induces cell death in certain cancer cell lines by interfering with the metabolism of the cancer cells. Therefore, understanding the mechanisms of action for metformin will provide insights into how to better treat diabetes and other metabolic disorders and also into the development of new therapeutic drugs...
April 26, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28443030/mitochondrial-reactive-oxygen-species-and-kidney-hypoxia-in-the-development-of-diabetic-nephropathy
#2
REVIEW
Tomas A Schiffer, Malou Friederich-Persson
The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28440488/dipeptidyl-peptidase%C3%A2-4-inhibitor-sitagliptin-prevents-high-glucose%C3%A2-induced-apoptosis-via-activation-of-amp%C3%A2-activated-protein-kinase-in-endothelial-cells
#3
Chao Wu, Shunying Hu, Nanping Wang, Jianwei Tian
Diabetes mellitus (DM), which is a chronic metabolic disorder, is the primary risk factor of life‑threatening vascular complications. Endothelial apoptosis is important in the development of the initial vascular lesion preceding the diabetic disease. Sitagliptin is a dipeptidyl peptidase‑4 (DPP‑4) inhibitor and extensively used in the clinical treatment of DM. DPP‑4 inhibitors have been demonstrated to be beneficial in the improvement of endothelial homeostasis, however the molecular mechanism by which they exhibit these effects remains to be elucidated...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440430/perfluorooctanoic-acid-induces-oxidative-damage-and-mitochondrial-dysfunction-in-pancreatic-%C3%AE-cells
#4
Kwang Sik Suh, Eun Mi Choi, Yu Jin Kim, Soo Min Hong, So Yong Park, Sang Youl Rhee, Seungjoon Oh, Sung Woon Kim, Youngmi Kim Pak, Wonchae Choe, Suk Chon
Several environmental contaminants have been linked to the development of diabetes and increased diabetes‑associated mortality. Perfluorooctanoic acid (PFOA) is a widely used perfluoroalkane found in surfactants and lubricants, and in processing aids used in the production of polymers. Furthermore, PFOA has been detected in humans, wildlife and the environment. The present study investigated the toxic effects of PFOA on rat pancreatic β‑cell‑derived RIN‑m5F cells. Cell viability, apoptosis, reactive oxygen and nitrogen species, cytokine release and mitochondrial parameters, including membrane potential collapse, reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release were assessed...
April 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28439848/the-janus-head-of-oxidative-stress-in-metabolic-diseases-and-during-physical-exercise
#5
REVIEW
Dominik Pesta, Michael Roden
PURPOSE OF REVIEW: Oxidative stress describes an imbalance between production and degradation of reactive oxygen species (ROS), which can damage macromolecules. However, ROS may also serve as signaling molecules activating cellular pathways involved in cell proliferation and adaptation. This review describes alterations in metabolic diseases including obesity, insulin resistance, and/or diabetes mellitus as well as responses to acute and chronic physical exercise. RECENT FINDINGS: Chronic upregulation of oxidative stress associates with the development of insulin resistance and type 2 diabetes (T2D)...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28437656/a-gene-environment-interaction-analysis-of-plasma-selenium-with-prevalent-and-incident-diabetes-the-hortega-study
#6
Inmaculada Galan-Chilet, Maria Grau-Perez, Griselda De Marco, Eliseo Guallar, Juan Carlos Martin-Escudero, Alejandro Dominguez-Lucas, Isabel Gonzalez-Manzano, Raul Lopez-Izquierdo, Laisa Socorro Briongos-Figuero, Josep Redon, Felipe Javier Chaves, Maria Tellez-Plaza
BACKGROUND: Selenium and single-nucleotide-polymorphisms in selenoprotein genes have been associated to diabetes. However, the interaction of selenium with genetic variation in diabetes and oxidative stress-related genes has not been evaluated as a potential determinant of diabetes risk. METHODS: We evaluated the cross-sectional and prospective associations of plasma selenium concentrations with type 2 diabetes, and the interaction of selenium concentrations with genetic variation in candidate polymorphisms, in a representative sample of 1452 men and women aged 18-85 years from Spain...
April 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#7
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28435771/brown-adipose-tissue-bioenergetics-a-new-methodological-approach
#8
María Calderon-Dominguez, Martín Alcalá, David Sebastián, Antonio Zorzano, Marta Viana, Dolors Serra, Laura Herrero
The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT...
April 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28433632/role-of-microrna-130b-in-placental-pgc-1%C3%AE-tfam-mitochondrial-biogenesis-pathway
#9
Shaoning Jiang, April M Teague, Jeanie B Tryggestad, Steven D Chernausek
Diabetes during pregnancy is associated with abnormal placenta mitochondrial function and increased oxidative stress, which affect fetal development and offspring long-term health. Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis and energy metabolism. The molecular mechanisms underlying the regulation of PGC-1α in placenta in the context of diabetes remain unclear. The present study examined the role of microRNA 130b (miR-130b-3p) in regulating PGC-1α expression and oxidative stress in a placental trophoblastic cell line (BeWo)...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432299/tangluoning-a-traditional-chinese-medicine-attenuates-in-vivo-and-in-vitro-diabetic-peripheral-neuropathy-through-modulation-of-perk-nrf2-pathway
#10
Xinwei Yang, Weijie Yao, Haolong Liu, Yanbin Gao, Renhui Liu, Liping Xu
Prolonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress have been demonstrated to play a key role in progression of diabetic peripheral neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and endoplasmic reticulum (ER) stress which is associated with cell survival. This study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential in Schwann cells cultured in 150 mM glucose...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431037/gestational-diabetes-alters-functions-in-offspring-s-umbilical-cord-cells-with-implications-for-cardiovascular-health
#11
Ajith Isaac Amrithraj, Anjaneyulu Kodali, Linh Nguyen, Adrian Kee Keong Teo, Cheng Wei Chang, Neerja Karnani, Kai Lyn Ng, Peter D Gluckman, Yap Seng Chong, Walter Stünkel
As non-communicable diseases such as type 2 diabetes mellitus have their roots in prenatal development and conditions such as maternal gestational diabetes (GDM), we aimed to test this hypothesis in primary cells derived from the offspring of GDM mothers compared to control subjects. We have assessed primary umbilical cord derived cells such as human umbilical vein endothelial cells (HUVECs) and Wharton's jelly derived mesenchymal stem cells (WJMSCs) from both, the offspring of GDM and non-GDM mothers. We have compared the primary isolates in cell based assays measuring proliferation, mitochondrial oxygen consumption, and the ability to support blood vessel growth...
April 19, 2017: Endocrinology
https://www.readbyqxmd.com/read/28429253/modified-metformin-as-a-more-potent-anticancer-drug-mitochondrial-inhibition-redox-signaling-antiproliferative-effects-and-future-epr-studies
#12
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael B Dwinell
Metformin, one of the most widely prescribed antidiabetic drugs in the world, is being repurposed as a potential drug in cancer treatment. Epidemiological studies suggest that metformin exerts anticancer effects in diabetic patients with pancreatic cancer. However, at typical antidiabetic doses the bioavailability of metformin is presumably too low to exert antitumor effects. Thus, more potent analogs of metformin are needed in order to increase its anticancer efficacy. To this end, a new class of mitochondria-targeted metformin analogs (or mito-metformins) containing a positively-charged lipophilic triphenylphosphonium group was synthesized and tested for their antitumor efficacy in pancreatic cancer cells...
April 21, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28428363/phlpp-a-putative-cellular-target-during-insulin-resistance-and-type-2-diabetes
#13
Alpana Mathur, Vivek Kumar Pandey, Poonam Kakkar
Progressive research in the past decade converges to the impact of PHLPP (Pleckstrin homology domain and leucine rich repeat protein phosphatase) in regulating the cellular metabolism through PI3K/Akt inhibition. Defects in the PKB/Akt signaling coordinates with impaired insulin secretion and insulin resistance, identified during T2D, obesity and cardiovascular disorders which brings in the relevance of PHLPPs in the metabolic paradigm. In this review, we discuss the impact of PHLPP isoforms in insulin signaling and its associated cellular events including mitochondrial dysfunction, DNA damage, autophagy and cell death...
April 20, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28427390/advanced-glycation-end-products-decreases-expression-of-endothelial-nitric-oxide-synthase-through-oxidative-stress-in-human-coronary-artery-endothelial-cells
#14
Xiaomei Ren, Liqun Ren, Qin Wei, Hua Shao, Long Chen, Naifeng Liu
BACKGROUND: Advanced glycation end-products (AGEs) are elevated under diabetic conditions and associated with insulin resistance, endothelial dysfunction and vascular inflammation in humans. It has been demonstrated that AGEs evoke oxidative and inflammatory reactions in endothelial cells through the interaction with a receptor for AGEs (RAGE). Here, we aimed to identify the cellular mechanisms by which AGEs exacerbate the endothelial dysfunction in human coronary artery endothelial cells (HCAECs)...
April 20, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28425181/effects-of-different-aerobic-exercise-frequencies-on%C3%A2-streptozotocin-nicotinamide-induced-type-2-diabetic-rats-continuous-versus-short-bouts-and-weekend-warrior-exercises
#15
Nuray Alaca, Serap Uslu, Guldal Gulec Suyen, Umit Ince, Mustafa Serteser, Hızır Kurtel
BACKGROUND: Exercise training is known to exert multiple beneficial effects on type 2 diabetes mellitus (T2DM). In this study, we aimed at exploring the effects of aerobic exercise frequencies on diabetic parameters, the histopathological structure of skeletal muscle, diabetic myopathy and mitochondrial enzyme activities in an experimental model of T2DM. METHODS: T2DM was induced by using nicotinamide (110 mg/kg) and streptozotocin (65 mg/kg) in Sprague Dawley rats (n: 35)...
April 20, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28421204/diabetic-cardiomyopathy-current-approach-and-potential-diagnostic-and-therapeutic-targets
#16
REVIEW
Georgiana-Emmanuela Gilca, Gabriela Stefanescu, Oana Badulescu, Daniela-Maria Tanase, Iris Bararu, Manuela Ciocoiu
Although ischemic heart disease is the major cause of death in diabetic patients, diabetic cardiomyopathy (DCM) is increasingly recognized as a clinically relevant entity. Considering that it comprises a variety of mechanisms and effects on cardiac function, increasing the risk of heart failure and worsening the prognosis of this patient category, DCM represents an important complication of diabetes mellitus, with a silent development in its earlier stages, involving intricate pathophysiological mechanisms, including oxidative stress, defective calcium handling, altered mitochondrial function, remodeling of the extracellular matrix, and consequent deficient cardiomyocyte contractility...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28421194/dihydromyricetin-protects-against-diabetic-cardiomyopathy-in-streptozotocin-induced-diabetic-mice
#17
Bin Wu, Jie Lin, Jian Luo, Dong Han, Miaomiao Fan, Tao Guo, Ling Tao, Ming Yuan, Fu Yi
Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic patients. The present study sought to explore the potential effects of dihydromyricetin (DHM) on DCM and its possible mechanism. A diabetic model was induced by intraperitoneal injection of streptozotocin (STZ) in C57BL/6J mice. Two weeks after the STZ injection, mice were randomly allocated into the following 4 groups for treatment: the control group (CON), the control treated with DHM group (CON + DHM), the diabetes group (DM), and the diabetes treated with DHM group (DM + DHM)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28420087/skeletal-muscle-nucleo-mitochondrial-crosstalk-in-obesity-and-type-2-diabetes
#18
REVIEW
Prasad P Devarshi, Sean M McNabney, Tara M Henagan
Skeletal muscle mitochondrial dysfunction, evidenced by incomplete beta oxidation and accumulation of fatty acid intermediates in the form of long and medium chain acylcarnitines, may contribute to ectopic lipid deposition and insulin resistance during high fat diet (HFD)-induced obesity. The present review discusses the roles of anterograde and retrograde communication in nucleo-mitochondrial crosstalk that determines skeletal muscle mitochondrial adaptations, specifically alterations in mitochondrial number and function in relation to obesity and insulin resistance...
April 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#19
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28414198/ly333531-a-pkc%C3%AE-inhibitor-attenuates-glomerular-endothelial-cell-apoptosis-in-the-early-stage-of-mouse-diabetic-nephropathy-via-down-regulating-swiprosin-1
#20
Zhi-Bin Wang, Su Zhang, Ya Li, Rong-Mei Wang, Ling-Chang Tong, Yue Wang, Wei-Ye Liu, Ding-Feng Su, Ye Tu, Li-Chao Zhang, Ling Li
Glomerular endothelial cell (GEC) injury plays an important role in the early stage of diabetic nephropathy (DN). Previous studies show that a PKCβ inhibitor is effective for treating DN. In the current study we further explored the effects and molecular mechanisms of PKCβ inhibitors on GEC apoptosis in DN in streptozotocin-induced diabetic mice in vivo and high glucose- or PMA-treated human renal glomerular endothelial cells (HRGECs) in vitro. In the diabetic mice, hyperglycemia caused aggravated nephropathy and GEC apoptosis accompanied by significantly increased expression of swiprosin-1, a potentally pro-apoptotic protein...
April 17, 2017: Acta Pharmacologica Sinica
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