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Mitochondrial diabetes

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https://www.readbyqxmd.com/read/29679925/tocotrienol-rich-fraction-supplementation-reduces-hyperglycemia-induced-skeletal-muscle-damage-through-regulation-of-insulin-signaling-and-oxidative-stress-in-type-2-diabetic-mice
#1
Heaji Lee, Yunsook Lim
Chronic hyperglycemia induces impairment of muscle growth and development of diabetes mellitus (DM). Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility. In this study, we investigated the effect of tocotrienol-rich fraction (TRF) supplementation on skeletal muscle damage in diabetic mice. Diabetes was induced by a high-fat diet with streptozotocin (STZ) injection (100 mg/kg) in male C57BL/6J mice...
March 21, 2018: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29679277/the-role-of-mitochondrial-dna-damage-at-skeletal-muscle-oxidative-stress-on-the-development-of-type-2-diabetes
#2
Julia Matzenbacher Dos Santos, Denise Silva de Oliveira, Marcos Lazaro Moreli, Sandra Aparecida Benite-Ribeiro
Reduced cellular response to insulin in skeletal muscle is one of the major components of the development of type 2 diabetes (T2D). Mitochondrial dysfunction involves in the accumulation of toxic reactive oxygen species (ROS) that leads to insulin resistance. The aim of this study was to verify the involvement of mitochondrial DNA damage at ROS generation in skeletal muscle during development of T2D. Wistar rats were fed a diet containing 60% fat over 8 weeks and at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced)...
April 20, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29679259/dna-methylation-a-potential-source-of-mitochondria-dna-base-mismatch-in-the-development-of-diabetic-retinopathy
#3
Manish Mishra, Renu A Kowluru
In the development of diabetic retinopathy, retinal mitochondria are dysfunctional, and mitochondrial DNA (mtDNA) is damaged with increased base mismatches and hypermethylated cytosines. DNA methylation is also a potential source of mutation, and in diabetes, the noncoding region, the displacement loop (D-loop), experiences more methylation and base mismatches than other regions of the mtDNA. Our aim was to investigate a possible crosstalk between mtDNA methylation and base mismatches in the development of diabetic retinopathy...
April 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29678670/etiology-of-type-2-diabetes-and-alzheimer-s-disease-exploring-the-mitochondria
#4
REVIEW
Talisa K Silzer, Nicole R Phillips
Type 2 diabetes is a significant risk factor for developing Alzheimer's disease later in life, and particular populations have a disproportionate risk because of the high prevalence of type 2 diabetes. There are many overlapping pathologies, and teasing out the primary root cause, if one indeed exists, is very difficult. Here, we review (1) the key facets of mitochondrial biology that are relevant to the two conditions, and (2) the role that mitochondrial dysfunction plays in the shared pathophysiology. We posit that mitochondrial dysfunction lies at the root of the affected processes rather than alongside them as a co-pathology...
April 17, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29674631/orally-active-species-independent-novel-a-3-adenosine-receptor-antagonist-protects-against-kidney-injury-in-db-db-mice
#5
Debra Dorotea, Ahreum Cho, Gayoung Lee, Guideock Kwon, Junghwa Lee, Pramod K Sahu, Lak Shin Jeong, Dae Ryong Cha, Hunjoo Ha
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and the current pharmacological treatment for DKD is limited to renin-angiotensin system (RAS) inhibitors. Adenosine is detectable in the kidney and is significantly elevated in response to cellular damage. While all 4 known subtypes of adenosine receptors, namely, A1 AR, A2a AR, A2b AR, and A3 AR, are expressed in the kidney, our previous study has demonstrated that a novel, orally active, species-independent, and selective A3 AR antagonist, LJ-1888, ameliorates unilateral ureteral obstruction-induced tubulointerstitial fibrosis...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29674007/mst1-inhibits-sirt3-expression-and-contributes-to-diabetic-cardiomyopathy-through-inhibiting-parkin-dependent-mitophagy
#6
Shanjie Wang, Zhijing Zhao, Yanhong Fan, Mingming Zhang, Xinyu Feng, Jie Lin, Jianqiang Hu, Zheng Cheng, Chuang Sun, Tingting Liu, Zhenyu Xiong, Zhi Yang, Haichang Wang, Dongdong Sun
Mitochondrial dysfunction contributes to heart failure induced mortality in approximately 80% of diabetic patients. Mitophagy degrades defective mitochondria and maintains a healthy mitochondrial population, which is essential for cardiomyocyte survival in diabetic stress. Herein, we determined whether Mst1 regulated mitophagy and investigated the downstream signaling pathway in the development of diabetic cardiomyopathy (DCM). Mst1 deficiency promoted elimination of dysfunctional mitochondria in diabetic cardiomyopathy without affecting mitochondrial biogenesis...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29670917/pancreatic-beta-cell-death-novel-potential-mechanisms-in-diabetes-therapy
#7
REVIEW
Joselyn Rojas, Valmore Bermudez, Jim Palmar, María Sofía Martínez, Luis Carlos Olivar, Manuel Nava, Daniel Tomey, Milagros Rojas, Juan Salazar, Carlos Garicano, Manuel Velasco
Purpose of Review: Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. Recent Findings: Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29666899/altered-mitochondrial-bioenergetics-and-ultrastructure-in-the-skeletal-muscle-of-young-adults-with-type-1-diabetes
#8
Cynthia M F Monaco, Meghan C Hughes, Sofhia V Ramos, Nina E Varah, Christian Lamberz, Fasih A Rahman, Chris McGlory, Mark A Tarnopolsky, Matthew P Krause, Robert Laham, Thomas J Hawke, Christopher G R Perry
AIMS/HYPOTHESIS: A comprehensive assessment of skeletal muscle ultrastructure and mitochondrial bioenergetics has not been undertaken in individuals with type 1 diabetes. This study aimed to systematically assess skeletal muscle mitochondrial phenotype in young adults with type 1 diabetes. METHODS: Physically active, young adults (men and women) with type 1 diabetes (HbA1c 63.0 ± 16.0 mmol/mol [7.9% ± 1.5%]) and without type 1 diabetes (control), matched for sex, age, BMI and level of physical activity, were recruited (n = 12/group) to undergo vastus lateralis muscle microbiopsies...
April 18, 2018: Diabetologia
https://www.readbyqxmd.com/read/29665656/forskolin-protects-against-cisplatin-induced-ototoxicity-by-inhibiting-apoptosis-and-ros-production
#9
Xiangrui Guo, Xiaohui Bai, Li Li, Jianfeng Li, Haibo Wang
Cisplatin is widely used in the treatment of various types of cancer. However, it could cause severe side effects such as ototoxicity, which greatly limit the clinical application of cisplatin. Forskolin (FSK) is a diterpene derived from the plant Coleus forskohlii, and has been proven an effective drug for cardiovascular disease, diabetes, and asthma because of its anti-oxidant and anti-inflammatory action. Here, we investigated the effects of FSK in cisplatin-induced ototoxicity, and we found that FSK could significantly protect against cisplatin-induced ototoxicity in both cell line and isolated mouse cochlear...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29663489/high-glucose-induced-excessive-reactive-oxygen-species-promote-apoptosis-through-mitochondrial-damage-in-rat-cartilage-endplate-cells
#10
Zengxin Jiang, Wei Lu, Qingmin Zeng, Defang Li, Lei Ding, Jingping Wu
PURPOSE: Diabetes mellitus (DM) is an important factor in intervertebral disc degeneration (IDD). Apoptosis of cartilage endplate (CEP) cells is one of the initiators of IDD. However, the effects of high glucose on CEP cells are still unknown. Therefore, we conducted the present study to evaluate the effects of high glucose on CEP cells and to identify the mechanisms of those effects. METHODS: Rat CEP cells were isolated and cultured in 10% foetal bovine serum (FBS, normal control) or high-glucose medium (10% FBS + 0...
April 16, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29660466/formononetin-an-isoflavone-from-astragalus-membranaceus-inhibits-proliferation-and-metastasis-of-ovarian-cancer-cells
#11
Jing Zhang, Likun Liu, Jing Wang, Baoyin Ren, Lin Zhang, Weiling Li
ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus which was originally described in the Shennong's Classic of Materia Medica, the earliest complete Pharmacopoeia of China written from the Warring States Period to Han Dynasty, has been widely used in Chinese medicine for>2,000 years, especially in the prescription of curing cancer. A. membranaceus has various bioactivities, such as anti-tumor, anti-viral, anti-oxidant, anti-diabetes, anti-inflammation, anti-atherosclerosis, immunomodulation, hepatoprotection, hematopoiesis, neuroprotection and so on...
April 13, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29660213/role-of-ncor1-in-mitochondrial-function-and-energy-metabolism
#12
REVIEW
Tanes I Lima, Rafael R Valentim, Hygor N Araújo, André G Oliveira, Bianca C Favero, Eveline S Menezes, Rafaela Araújo, Leonardo R Silveira
Mitochondrial number and shape are constantly changing in response to increased energy demands. The ability to synchronize mitochondrial pathways to respond to energy fluctuations within the cell is a central aspect of mammalian homeostasis. This dynamic process depends on the coordinated activation of transcriptional complexes to promote the expression of genes encoding for mitochondrial proteins. Recent evidence has shown that the nuclear corepressor NCoR1 is an essential metabolic switch which acts on oxidative metabolism signaling...
April 16, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#13
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29658312/mice-pancreatic-islets-protection-from-oxidative-stress-induced-by-single-walled-carbon-nanotubes-through-naringin
#14
A Ahangarpour, S Alboghobeish, A A Oroojan, M A Dehghani
The growing use of carbon nanotubes (CNTs) emphasizes the importance of its potential toxic effects on the human health. Previous studies proved that CNTs caused oxidative stress and decreased cell viability. On the other hand, reactive oxygen species (ROS) and oxidative stress impaired β-cell functions and reduced the insulin secretion. However, there is not any study on the effects of CNTs on islets and β-cells. Therefore, the present study aimed to evaluate the effects of single-walled CNTs (SWCNTs) on oxidative stress in islets in addition to the protective effects of naringin (NRG) as an antioxidant ...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29656110/targeting-hepatic-pyruvate-dehydrogenase-kinases-restores-insulin-signaling-and-mitigates-chrebp-mediated-lipogenesis-in-diet-induced-obese-mice
#15
Cheng-Yang Wu, Shih-Chia Tso, Jacinta L Chuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David T Chuang
OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4 expression is tightly associated with obesity and diabetes. In this investigation, we test the central hypothesis that PDKs1-4 are a pharmacological target for lowering glucose levels and restoring insulin sensitivity in obesity and type 2 diabetes (T2D)...
March 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29651255/sex-specific-skeletal-muscle-fatigability-and-decreased-mitochondrial-oxidative-capacity-in-adult-rats-exposed-to-postnatal-hyperoxia
#16
Laura H Tetri, Gary M Diffee, Gregory P Barton, Rudolf K Braun, Hannah E Yoder, Kristin Haraldsdottir, Marlowe W Eldridge, Kara N Goss
Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29649104/coordination-of-gpr40-and-ketogenesis-signaling-by-medium-chain-fatty-acids-regulates-beta-cell-function
#17
Julien Benjamin Pujol, Nicolas Christinat, Yann Ratinaud, Claudia Savoia, Siobhan E Mitchell, El Hadji M Dioum
Diabetes prevalence increases with age, and β-cell dysfunction contributes to the incidence of the disease. Dietary lipids have been recognized as contributory factors in the development and progression of the disease. Unlike long chain triglycerides, medium chain triglycerides (MCT) increase fat burning in animal and human subjects as well as serum C-peptide in type 2 diabetes patients. We evaluated the beneficial effects of MCT on β-cells in vivo and in vitro. MCT improved glycemia in aged rats via β-cell function assessed by measuring insulin secretion and content...
April 12, 2018: Nutrients
https://www.readbyqxmd.com/read/29644834/31p-mr-spectroscopy-of-patients-with-mild-and-serious-lower-limb-ischemia
#18
Petr Sedivy, Miloslav Drobny, Monika Dezortova, Vit Herynek, Karel Roztocil, Helena Cermakova, Andrea Nemcova, Michal Dubsky, Milan Hajek
BACKGROUND: 31P MR spectroscopy is a technique for undertaking a comprehensive evaluation of muscle metabolism. The goal of this study was to compare patients with mild and severe lower limb ischemia measured by 31P MR spectroscopy at rest and during exercise. METHODS: 16 nondiabetic mild peripheral arterial occlusive disease (PAOD) patients, 23 diabetic PAOD patients with severe ischemia and 19 healthy controls were examined by rest and dynamic 31P MR spectroscopy with a 3T MR system equipped with an MR-compatible home-made pedal ergometer...
April 11, 2018: International Angiology: a Journal of the International Union of Angiology
https://www.readbyqxmd.com/read/29643061/supplemental-oxygen-improves-in-vivo-mitochondrial-oxidative-phosphorylation-flux-in-sedentary-obese-adults-with-type-2-diabetes
#19
Melanie Cree-Green, Rebecca L Scalzo, Kylie Harrall, Bradley R Newcomer, Irene E Schauer, Amy G Huebschmann, Shawna McMillin, Mark S Brown, David Orlicky, Leslie Knaub, Kristen J Nadeau, P Mason Mcclatchey, Timothy A Bauer, Judith G Regensteiner, Jane E B Reusch
Type 2 diabetes is associated with impaired exercise capacity. Alterations in both muscle perfusion and mitochondrial function can contribute to exercise impairment. We hypothesized that impaired muscle mitochondrial function in type 2 diabetes is mediated, in part, by decreased tissue oxygen delivery and would improve with oxygen supplementation. Ex vivo muscle mitochondrial content and respiration assessed from biopsy samples demonstrated expected differences in obese individuals with (N=18) and without (N=17) diabetes...
April 11, 2018: Diabetes
https://www.readbyqxmd.com/read/29629372/glomerular-endothelial-cells-stress-and-cross-talk-with-podocytes-in-the-development-of-diabetic-kidney-disease
#20
REVIEW
Ilse Sofia Daehn
Diabetic kidney disease (DKD) is one of the major causes of morbidity and mortality in diabetic patients and also the leading single cause of end-stage renal disease in the United States. A large proportion of diabetic patients develop DKD and others don't, even with comparable blood glucose levels, indicating a significant genetic component of disease susceptibility. The glomerulus is the primary site of diabetic injury in the kidney, glomerular hypertrophy and podocyte depletion are glomerular hallmarks of progressive DKD, and the degree of podocyte loss correlates with severity of the disease...
2018: Frontiers in Medicine
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