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Mitochondrial diabetes

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https://www.readbyqxmd.com/read/29453877/significance-of-mitochondria-on-cardiometabolic-syndromes
#1
REVIEW
Nair Anupama, G Sindhu, K G Raghu
Metabolic syndromes (MS) are a cluster of disorders like obesity, hypertension, dyslipidemia, and diabetes. Cardiometabolic syndrome (CMS), a branch of MS, is a group of diseases affecting cardiovascular, renal, metabolic, prothrombotic and inflammatory abnormalities due to defects in energy metabolism. Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defect in the 1980s, research advances has revealed a number of common human disease involving mitochondrial dysfunction...
February 17, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29450720/diabetic-kidney-disease-is-there-a-role-for-glycemic-variability
#2
REVIEW
Savitha Subramanian, Irl B Hirsch
PURPOSE OF REVIEW: Diabetes is the leading cause of kidney disease globally. Diabetic kidney disease (DKD) is a heterogeneous disorder manifested as albuminuria and/or decreasing GFR. Hyperglycemic burden is the major contributor to the development of DKD. In this article, we review the evidence for the contribution of glycemic variability and the pitfalls associated with use of hemoglobin A1c (A1C), the gold standard for assessment of glucose control, in the setting of DKD. RECENT FINDINGS: Glycemic variability, characterized by swings in blood glucose levels, can result in generation of mitochondrial reactive oxygen species, a putative inciting factor for hyperglycemia-induced alterations in intracellular metabolic pathways...
February 15, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29449364/diabetic-cardiomyopathy-an-update-of-mechanisms-contributing-to-this-clinical-entity
#3
REVIEW
Guanghong Jia, Michael A Hill, James R Sowers
Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy...
February 16, 2018: Circulation Research
https://www.readbyqxmd.com/read/29448286/-mitochondrial-dysfunctions-and-role-of-coenzyme-q10-in-patients-with-glaucoma
#4
Carl Erb, Katarzyna Konieczka
Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA)...
February 2018: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/29447380/sirtuins-in-gamete-biology-and-reproductive-physiology-emerging-roles-and-therapeutic-potential-in-female-and-male-infertility
#5
Carla Tatone, Giovanna Di Emidio, Arcangelo Barbonetti, Gaspare Carta, Alberto M Luciano, Stefano Falone, Fernanda Amicarelli
BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of fertility emerged in 2003 when a defective reproductive phenotype was observed in SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been increasing in the last years, a recent comprehensive update on this issue is still lacking...
February 13, 2018: Human Reproduction Update
https://www.readbyqxmd.com/read/29446731/vitamin-d-receptor-a-novel-therapeutic-target-for-kidney-diseases
#6
Shikun Yang, Aimei Li, JianWen Wang, Jun Liu, Yachun Han, Wei Zhang, Yan Chun Li, Hao Zhang
BACKGROUND: Kidney disease is a serious problem that adversely affects human health, but critical knowledge is lacking on how to effectively treat established chronic kidney disease. Mounting evidence from animal and clinical studies has suggested that vitamin D receptor (VDR) activation has beneficial effects on various renal diseases. METHOD: A structured search of published research literature regarding VDR structure and function, VDR in various renal diseases (e...
February 14, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29445145/canagliflozin-mediated-dual-inhibition-of-mitochondrial-glutamate-dehydrogenase-and-complex-i-an-off-target-adverse-effect
#7
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29443067/high-resolution-respirometry-to-measure-mitochondrial-function-of-intact-beta-cells-in-the-presence-of-natural-compounds
#8
Kyle B Kener, Devin J Munk, Chad R Hancock, Jeffery S Tessem
High-resolution respirometry allows for the measurement of oxygen consumption of isolated mitochondria, cells and tissues. Beta cells play a critical role in the body by controlling blood glucose levels through insulin secretion in response to elevated glucose concentrations. Insulin secretion is controlled by glucose metabolism and mitochondrial respiration. Therefore, measuring intact beta cell respiration is essential to be able to improve beta cell function as a treatment for diabetes. Using intact 832/13 INS-1 derived beta cells we can measure the effect of increasing glucose concentration on cellular respiration...
January 23, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29439250/hoxa5-promotes-adipose-differentiation-via-increasing-dna-methylation-level-and-inhibiting-pka-hsl-signal-pathway-in-mice
#9
Weina Cao, Yatao Xu, Dan Luo, Muhammad Saeed, Chao Sun
BACKGROUND/AIMS: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms...
February 7, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29436377/elevated-medium-chain-acylcarnitines-are-associated-with-gestational-diabetes-and-early-progression-to-type-2-diabetes-and-induce-pancreatic-%C3%AE-cell-dysfunction
#10
Battsetseg Batchuluun, Dana Al Rijjal, Kacey J Prentice, Judith A Eversley, Elena Burdett, Haneesha Mohan, Alpana Bhattacharjee, Erica P Gunderson, Ying Liu, Michael B Wheeler
Specific circulating metabolites have emerged as important risk factors for the development of diabetes. The acylcarnitines (acylCs) are a family of metabolites known to be elevated in type-2 diabetes (T2D) and linked to peripheral insulin resistance. However, the impact of AcylCs on pancreatic β-cell function is not well understood. Here, we profiled circulating acylCs in two diabetes cohorts: 1) women with gestational diabetes (GDM) and 2) women with recent GDM who later developed impaired glucose tolerance (IGT), new-onset T2D or returned to normoglycemia within a two-year follow-up period...
February 7, 2018: Diabetes
https://www.readbyqxmd.com/read/29436254/therapeutic-targets-for-altering-mitochondrial-dysfunction-associated-with-diabetic-retinopathy
#11
Renu A Kowluru, Manish Mishra
Retinopathy remains as one of the most feared blinding complications of diabetes, and with the prevalence of this life-long disease escalating at an alarming rate, the incidence of retinopathy is also climbing. Although the cutting edge research has identified many molecular mechanisms associated with its development, the exact mechanism how diabetes damages the retina remains obscure, limiting therapeutic options for this devastating disease. Areas covered: This review focuses on the central role of mitochondrial dysfunction/damage in the pathogenesis of diabetic retinopathy, and how damaged mitochondria initiates a self-perpetuating vicious cycles of free radicals...
February 13, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29434648/hsp90%C3%AE-knockdown-in-dio-mice-reverses-insulin-resistance-and-improves-glucose-tolerance
#12
Enxuan Jing, Pragalath Sundararajan, Ishita Deb Majumdar, Suwagmani Hazarika, Samantha Fowler, Angela Szeto, Stephane Gesta, Armando J Mendez, Vivek K Vishnudas, Rangaprasad Sarangarajan, Niven R Narain
Background: Inhibition of Hsp90 has been shown to improve glucose tolerance and insulin sensitivity in mouse models of diabetes. In the present report, the specific isoform Hsp90ab1, was identified as playing a major role in regulating insulin signaling and glucose metabolism. Methods: In a diet-induced obese (DIO) mouse model of diabetes, expression of various Hsp90 isoforms in skeletal tissue was examined. Subsequent experiments characterized the role of Hsp90ab1 isoform in glucose metabolism and insulin signaling in primary human skeletal muscle myoblasts (HSMM) and a DIO mouse model...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29432738/humanin-promotes-mitochondrial-biogenesis-in-pancreatic-min6-%C3%AE-cells
#13
Qingqing Qin, Jieqiong Jin, Fang He, Yongqin Zheng, Tingting Li, Yun Zhang, Jundong He
Mitochondrial dysfunction is associated with β-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic β-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 β-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C...
February 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29431147/the-pathogenetic-role-of-%C3%AE-cell-mitochondria-in-type-2-diabetes
#14
REVIEW
Malin Fex, Lisa M Nicholas, Neelanjan Vishnu, Anya Medina, Vladimir V Sharoyko, David G Nicholls, Peter Spégel, Hindrik Mulder
Mitochondrial metabolism is a major determinant of insulin secretion from pancreatic β-cells. Type 2 diabetes evolves when β-cells fail to release appropriate amounts of insulin in response to glucose. This results in hyperglycemia and metabolic dysregulation. Evidence has recently been mounting that mitochondrial dysfunction plays an important role in these processes. Monogenic dysfunction of mitochondria is a rare condition but causes a type 2 diabetes-like syndrome owing to β-cell failure. Here, we describe novel advances in research on mitochondrial dysfunction in the β-cell in type 2 diabetes, with a focus on human studies...
March 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/29423103/metformin-induces-distinct-bioenergetic-and-metabolic-profiles-in-sensitive-versus-resistant-high-grade-serous-ovarian-cancer-and-normal-fallopian-tube-secretory-epithelial-cells
#15
Melissa Hodeib, Martin P Ogrodzinski, Laurent Vergnes, Karen Reue, Beth Y Karlan, Sophia Y Lunt, Paul-Joseph P Aspuria
Metformin is a widely used agent for the treatment of diabetes and infertility, however, it has been found to have anti-cancer effects in a variety of malignancies including high grade serous ovarian cancer (HGSC). Studies describing the mechanisms by which metformin affects HGSC are ongoing, but detailed analysis of its effect on the cellular metabolism of both HGSC cells and their precursor, normal fallopian tube secretory epithelial cells (FTSECs), is lacking. We addressed the effects of metformin and the more potent biguanide, phenformin, on HGSC cell lines and normal immortalized FTSECs...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29422990/polycystic-ovary-syndrome-in-mitochondrial-disorders-due-mtdna-or-ndna-variants
#16
REVIEW
Josef Finsterer, Sinda Zarrouk-Mahjoub
OBJECTIVES: Whether polycystic ovary syndrome (PCOS) is associated with mtDNA or nDNA mutations causing mitochondrial disorders (MIDs) or not is under debate. This review aims at summarising and discussing previous and recent findings concerning the frequency, diagnosis, and treatment of PCOS in MIDs. METHODS: Systematic literature review using appropriate search terms. RESULTS: Currently, no reports are available which document a causal relation between PCOS and specific or non-specific MIDs...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29415895/intracellular-localization-of-diacylglycerols-and-sphingolipids-influences-insulin-sensitivity-and-mitochondrial-function-in-human-skeletal-muscle
#17
Leigh Perreault, Sean A Newsom, Allison Strauss, Anna Kerege, Darcy E Kahn, Kathleen A Harrison, Janet K Snell-Bergeon, Travis Nemkov, Angelo D'Alessandro, Matthew R Jackman, Paul S MacLean, Bryan C Bergman
BACKGROUND: Accumulation of diacylglycerol (DAG) and sphingolipids is thought to promote skeletal muscle insulin resistance by altering cellular signaling specific to their location. However,the subcellular localization of bioactive lipids in human skeletal muscle is largely unknown. METHODS: We evaluated subcellular localization of skeletal muscle DAGs and sphingolipids in lean individuals (n = 15), endurance-trained athletes (n = 16), and obese men and women with (n = 12) and without type 2 diabetes (n = 15)...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29415201/genetic-variation-in-foxo3-is-associated-with-self-rated-health-in-a-population-based-sample-of-older-individuals
#18
Anna Zettergren, Silke Kern, Lina Rydén, Svante Östling, Kaj Blennow, Henrik Zetterberg, Hanna Falk, Ingmar Skoog
Self-rated health (SRH) strongly predicts mortality. Twin studies estimate that genetic factors account for a substantial part of the variability in SRH. Variations in the gene FOXO3 (forkhead box O3), and in genes located at the APOE (apoplipoprotein E) locus, are associated with longevity. This study explores the relationship between SRH and genetic variation related to longevity, in a population-based cohort of older individuals. SRH was assessed among 1520 individuals aged 75 to 87, and five single nucleotide polymorphisms (SNPs), in APOE, TOMM40 (translocase of outer mitochondrial membrane 40 homolog), and FOXO3 were genotyped...
February 5, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29413990/mitochondrial-gene-expression-changes-in-cultured-human-skin-cells-following-simulated-sunlight-irradiation
#19
J Kelly, J E Murphy
BACKGROUND: Exposure of skin to simulated sunlight irradiation (SSI) has being extensively researched and shown to be the main cause for changes in the skin including changes in cellular function and generation of reactive oxygen species (ROS). This oxidative stress can subsequently exert downstream effects and the subcellular compartments most affected by this oxidative stress are mitochondria. The importance of functional mitochondrial morphology is apparent as morphological defects are related to many human diseases including diabetes mellitus, liver disease, neurodegenerative diseases, aging and cancer...
November 10, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/29411334/regulation-and-bioactivity-of-the-ccn-family-of-genes-and-proteins-in-obesity-and-diabetes
#20
REVIEW
Stephen M Twigg
Across the years the CCNs have been increasingly implicated in the development of obesity, diabetes and its complications. Evidence for this is currently derived from their dysregulation in key metabolic pathological states in humans, animal and in vitro models, and also pre-clinical effects of their bioactivities. CCN2 is the best studied in this disease process and the other CCNs are yet to be better defined. Key steps where CCNs may play a pathogenic metabolic role include: (i) obesity and insulin resistance, where CCN2 inhibits fat cell differentiation in vitro and CCN3 may induce obesity and insulin resistance; (ii) elevated blood glucose levels to diabetes mellitus onset, where CCN2 may contribute to pancreatic beta cell and islet function; and (iii) in diabetes complications, such as nephropathy, retinopathy, liver disease (NAFLD/NASH), CVD and diabetes with heart failure...
February 6, 2018: Journal of Cell Communication and Signaling
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