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Corina T Madreiter-Sokolowski, Armin A Sokolowski, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS) ensures a supply of adenosine triphosphate (ATP), but is also the main source of potentially harmful levels of reactive oxygen species (ROS)...
March 16, 2018: Genes
Claire Greenhill
No abstract text is available yet for this article.
March 16, 2018: Nature Reviews. Endocrinology
Lisa Menegazzo, Valentina Scattolini, Roberta Cappellari, Benedetta Maria Bonora, Mattia Albiero, Mario Bortolozzi, Filippo Romanato, Giulio Ceolotto, Saula Vigili de Kreutzeberg, Angelo Avogaro, Gian Paolo Fadini
AIMS: Diabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis. METHODS: We measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin...
March 15, 2018: Acta Diabetologica
Jesús Emilo Quintero Ojeda, Maribel Aguilar-Medina, Vicente Olimón-Andalón, Rosa Alicia García Jau, Alfredo Ayala Ham, José Geovanni Romero Quintana, Erika de Lourdes Silva-Benítez, Guzmán Sanchez-Schmitz, Rosalío Ramos-Payán
Diabetes mellitus (DM) is a metabolic disease characterized by persistent high levels of glucose in plasma. Chronic hyperglycemia is thought to increase oxidative stress and the formation of free radicals that in turn damage cells. Thus, we decided to determine the frequency of nuclear abnormalities in epithelial cells from cheek and tongue mucosa of DM patients with type 1 (DM1, treated only with insulin) and type 2 (DM2, treated with metformin) using the buccal micronucleus cytome (BMCyt) assay. Micronuclei frequency in cheek epithelial cells was higher in both DM1 (0...
2018: BioMed Research International
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Sen Xu, Zong-Yuan Yang, Ping Jin, Xin Yang, Xiaoting Li, Xiao Wei, Ya Wang, Sixiang Long, Taoran Zhang, Gang Chen, Chaoyang Sun, Ding Ma, Qinglei Gao
Ovarian cancer (OC) is a devastating disease due to its high incidence of relapse and chemoresistance. The tumor microenvironment, especially the tumor stroma compartment, was proven to contribute tremendously to the unsatisfactory chemotherapeutic efficacy in OC. Cytotoxic agents not only effect tumor cells, but also modulate the phenotype and characteristics of the vast stromal cell population, which can in turn alter the tumor cell response to chemointervention. In this study, we focused on the tumor stroma response to cytotoxic agents and the subsequent effect on the OC tumor cells...
March 15, 2018: Molecular Cancer Therapeutics
Misbah Malik, Nasira Tasnim, Ghazala Mahmud
OBJECTIVE: To determine the efficacy of metformin alone versus metformin plus simvastatin for treatment of polycystic ovariansyndrome (PCOS). STUDY DESIGN: Randomized controlled trial. PLACE AND DURATION OF STUDY: Maternal and Child Health Centre, Unit II, Pakistan Institute of Medical Sciences (PIMS), from November 2014 to April 2015. METHODOLOGY: One hundred and eight patients (108) were randomly divided into metformin group (n=54) and metformin plus simvastatin group (n=54), detailed clinical history, including menstrual details, was taken with thorough examination performed...
March 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Antonio Gil-Gomez, Ana Isabel Gómez-Sotelo, Isidora Ranchal, Ángela Rojas, Marta García-Valdecasas, Rocío Muñoz-Hernández, Rocío Gallego-Durán, Javier Ampuero, Manuel Romero Gómez
AIM: to analyze the effect of metformin on ammonia production derived from glutamine metabolism in vitro and in vivo. METHODS: twenty male Wistar rats were studied for 28 days after a porto-caval anastomosis (n = 16) or a sham operation (n = 4). Porto-caval shunted animals were randomized into two groups (n = 8) and either received 30 mg/kg/day of metformin for two weeks or were control animals. Plasma ammonia concentration, Gls gene expression and K-type glutaminase activity were measured in the small intestine, muscle and kidney...
March 15, 2018: Revista Española de Enfermedades Digestivas
Xuan Du, Wen Lu, Zijun Lu, Xinyu Shao, Chunhong Hu, Bimin Shi
Background: To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods: 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups...
2018: Journal of Diabetes Research
Liisa Ailanen, Natalia N Bezborodkina, Laura Virtanen, Suvi T Ruohonen, Anastasia V Malova, Sergey V Okovityi, Elizaveta Y Chistyakova, Eriika Savontaus
Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPYD βH ) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance...
April 2018: Pharmacology Research & Perspectives
Balraj Singh, Vanessa N Sarli, Laura J Washburn, Milan R Raythatha, Anthony Lucci
We previously described a strategy for selecting highly adaptable rare triple-negative breast cancer (TNBC) cells based on their ability to survive a severe and prolonged metabolic challenge, e.g., a lack of glutamine. We hypothesized that metabolically adaptable (MA) cancer cells selected from the SUM149 cell line in this manner have the capacity to survive a variety of challenges that postulated "decathlon winner" cancer cells must survive to succeed in metastasis. These MA cells were resistant to glutaminase inhibitor CB-839, as predicted from their ability to proliferate without exogenous glutamine...
February 16, 2018: Oncotarget
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
Ye-Jin Lee, Sung Koo Han, Ju Hee Park, Jung Kyu Lee, Deog Keom Kim, Hee Soon Chung, Eun Young Heo
Background/Aims: Patients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM. Methods: This retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012...
March 16, 2018: Korean Journal of Internal Medicine
Olga Montvida, Jonathan Shaw, Lawrence Blonde, Sanjoy K Paul
AIMS: To inform patients and their carers about the probability of reducing HbA1c to clinically desirable levels and sustainability of such control over 2 years with major second-line anti-diabetic therapies under individual risk scenario, with and without third-line intensification. MATERIALS AND METHODS: From US Centricity Electronic Medical Records, 163,081 patients with type 2 diabetes aged 18-80 years, who initiated metformin; intensified with DPP-4 inhibitor (DPP-4i), GLP-1 receptor agonist (GLP-1RA), sulfonylurea, insulin, or thiazolidinedione; and continued second-line ≥ 6 month, were selected...
March 14, 2018: Diabetes, Obesity & Metabolism
Robert A Bailey, Alicia C Shillington, Qing Harshaw, Martha M Funnell, Jeffrey VanWingen, Nananda Col
INTRODUCTION: Failure to intensify treatment for type 2 diabetes mellitus (T2DM) when indicated, or clinical inertia, is a major obstacle to achieving optimal glucose control. This study investigates the impact of a values-focused patient decision aid (PDA) for T2DM antihyperglycemic agent intensification on patient values related to domains important in decision-making and preferred treatments. METHODS: Patients with poorly controlled T2DM who were taking a metformin-containing regimen were recruited through physicians to access a PDA presenting evidence-based information on T2DM and antihyperglycemic agent class options...
March 13, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Sanjay Kalra, Jubbin Jacob, Manash P Baruah
Salutogenesis is an accepted approach for chronic disease management. Calorie restriction and exercise are two evidence based salutogenic interventions in diabetes treatment. Calorie restriction mimetics and exercise mimetics may be used as pharmacological tools to help manage diabetes in a sulutogenic manner. This article discusses the biochemical basis and pharmacology of metformin and sodium glucose cotransporter 2 inhibitors. It describes how a combination of these drugs can be used as a calories restriction and exercise mimetic, to help improve diabetes control...
January 2018: Indian Journal of Endocrinology and Metabolism
Eunyoung Bang, Boyoung Lee, Joon-Oh Park, Yooncheol Jang, Aekyong Kim, Sungwuk Kim, Hee-Sup Shin
In recent years, as the aging population grows, aging-induced cognitive impairments including dementia and Alzheimer's disease (AD) have become the biggest challenges for global public health and social care. Therefore, the development of potential therapeutic drugs for aging-associated cognitive impairment is essential. Metabolic dysregulation has been considered to be a key factor that affects aging and dementia. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a primary sensor of cellular energy states and regulates cellular energy metabolism...
February 2018: Experimental Neurobiology
Gang Guo, Moushun Fu, Shuxiang Wei, Ruiwan Chen
Background: Diabetes mellitus (DM) has been identified to be both a risk factor and a prognostic factor in a variety of malignancies, but its association with the risk and outcome of nasopharyngeal carcinoma (NPC) is still unclear. To elucidate this issue, we systematically reviewed the evidence concerning the association between DM status and NPC. Materials and methods: We identified studies by a literature search of PubMed, Embase, and ISI Web of Knowledge through May 31, 2017, and by searching the reference lists of pertinent articles...
2018: OncoTargets and Therapy
Min Hu, Yuehui Zhang, Jiaxing Feng, Xue Xu, Jiao Zhang, Wei Zhao, Xiaozhu Guo, Juan Li, Edvin Vestin, Peng Cui, Xin Li, Xiaoke Wu, Mats Brannstrom, Linus R Shao, Hakan Billig
Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance...
March 13, 2018: Journal of Endocrinology
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