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https://www.readbyqxmd.com/read/28931178/the-oral-dipeptidyl-peptidase-4-inhibitor-sitagliptin-increases-circulating-levels-of-stromal-derived-factor-1-alpha
#1
Athanasia K Papazafiropoulou, Nikolaos Papanas, Aikaterini Trikkalinou, Evaggelos Fousteris, Andreas Melidonis
Recent studies have demonstrated that stromal derived factor-1α (SDF-1α) is a substrate of dipeptidyl-peptidase-4 (DPP-4) inhibitors. It has also been shown that SDF-1α shares anti-apoptotic as well as nephroprotective properties and exerts a beneficial effect in the cardiovascular system. Therefore, the aim of this study was to estimate the effect of treatment with the DDP-4 inhibitor sitagliptin on SDF-1α levels in subjects with type 2 diabetes mellitus (T2D). Overall, 32 patients (16 males) with T2D, mean age (±SD) 67...
September 20, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28930827/comparative-efficacy-and-safety-of-oral-antidiabetic-drugs-and-insulin-in-treating-gestational-diabetes-mellitus-an-updated-prisma-compliant-network-meta-analysis
#2
Hui-Ling Liang, Shu-Juan Ma, Yan-Ni Xiao, Hong-Zhuan Tan
BACKGROUND: The safety and efficacy of different drugs in treatment of gestational diabetes mellitus (GDM) patients who could not maintain normal glucose level only through diet and exercise remains to be debated. We performed this network meta-analysis (NAM) to compare and rank different antidiabetic drugs in glucose level control and pregnancy outcomes in GDM patients. METHODS: We searched PubMed, Cochrane Library, Web of Science, and Embase up to December 31, 2016...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28930456/metformin-an-anthropogenic-contaminant-of-seidlitzia-rosmarinus-collected-in-a-desert-region-near-the-gulf-of-aqaba-sinai-peninsula
#3
Ahmed R Hassan, Salah M El-Kousy, Sayed A El-Toumy, Karla Frydenvang, Truong Thanh Tung, Jesper Olsen, John Nielsen, Søren Brøgger Christensen
A phytochemical investigation of Seidlitzia rosmarinus collected along the shoreline of the Gulf of Aqaba in the remote southern desert region of the Sinai peninsula has revealed the presence of the registered drug metformin (4). However, analysis of the (14)C content revealed the drug to be an anthropogenic contaminant. Consequently, natural product researchers should be aware that compounds isolated from plants might originate from environmental contamination rather than biosynthesis. The new natural product N-(4-hydroxyphenylethyl)-α-chloroferuloylamide was isolated as a mixture of the E and Z isomers along with a number of other well-established secondary metabolites...
September 20, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28928832/downregulation-of-rab27a-contributes-to-metformin-induced-suppression-of-breast-cancer-stem-cells
#4
Feixue Feng, Jianping Zhang, Xiaoxuan Fan, Fang Yuan, Yinghao Jiang, Ruihua Lv, Yanxia Ma
Cancer stem cells (CSCs) are associated with tumor initiation, therapeutic resistance, relapse and metastasis. However, the underlying mechanisms CSCs use to preserve stemness are not yet fully understood. The present study demonstrated that the expression of RAB27A, member RAS oncogene family (Rab27a), which was reported to promote tumor progression by upregulating exocytosis of extracellular vesicles, was higher in mammosphere cells than in adherent MDA-MB-231 breast cancer cells. Downregulation of Rab27A inhibited mammosphere formation by decreasing the proportion of CD44+CD24-/low cells of the MDA-MB-231 cell line...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927780/effects-of-metformin-on-proliferation-and-apoptosis-of-human-megakaryoblastic-dami-and-meg-01-cells
#5
Xue Liang, Peiyan Kong, Jin Wang, Yulin Xu, Chunfang Gao, Guozhen Guo
Metformin has received increasing attention for its potential anticancer activity against certain human leukemia cells, but its effects on human megakaryoblastic cells are unclear. This study aimed to investigate the effects of metformin on proliferation and apoptosis of human megakaryoblastic cells (Dami and MEG-01) and the underlying molecular mechanisms. CCK8 assay was employed to measure cell proliferation. Flow cytometry was adopted to detect cell apoptosis. Western blot was further employed to measure apoptosis-related proteins...
August 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28927103/lack-of-chemopreventive-efficacy-of-metformin-in-rodent-models-of-urinary-bladder-head-and-neck-and-colon-intestine-cancer
#6
Matthew D Thompson, Ronald A Lubet, David L Mccormick, Margie L Clapper, Ann M Bode, M Margaret Juliana, Fariba Moeinpour, Clinton J Grubbs
Metformin is a biguanide employed in treating type II diabetes. Its potential efficacy for treating cancer has been demonstrated epidemiologically (lower cancer incidence in metformin users compared with users of sulfonylureas or insulin) and mechanistically, primarily in cell culture. Metformin decreases the levels of insulin-like growth factor 1 and secondarily inhibits the mammalian target of rapamycin pathway to exhibit anticancer effects. The current study examined its cancer preventive efficacy in multiple standard in situ arising cancer models...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926868/polycystic-ovary-syndrome-pcos-in-juvenile-and-adult-type-1-diabetes-in-a-german-austrian-cohort
#7
Christina Reinauer, Esther Bollow, Elke Fröhlich-Reiterer, Katharina Laubner, Dominik Bergis, Christof Schöfl, Hans-Peter Kempe, Michael Hummel, Pia Hennes, Katja Gollisch, Holger Haberland, Nicolin Datz, Thomas Meissner, Reinhard W Holl
Context While an association between PCOS and type 2 diabetes is well established, to date there have been few data on clinical care of type 1 diabetes (T1D) patients with PCOS. Objective The aim of our study was to characterize T1D patients with the comorbidity of PCOS within the DPV cohort with regard to diabetes phenotype, therapy and metabolic control. Design and Setting Clinical data from the prospective German/Austrian DPV cohort on patients with T1D and documented PCOS (n=76) were compared to female T1D controls (n=32,566) in reproductive age...
September 19, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28926637/selective-cytotoxicity-of-the-anti-diabetic-drug-metformin-in-glucose-deprived-chicken-dt40-cells
#8
Kei Kadoda, Takahito Moriwaki, Masataka Tsuda, Hiroyuki Sasanuma, Masamichi Ishiai, Minoru Takata, Hiroshi Ide, Shin-Ichiro Masunaga, Shunichi Takeda, Keizo Tano
Metformin is a biguanide drug that is widely used in the treatment of diabetes. Epidemiological studies have indicated that metformin exhibits anti-cancer activity. However, the molecular mechanisms underlying this activity currently remain unclear. We hypothesized that metformin is cytotoxic in a tumor-specific environment such as glucose deprivation and/or low oxygen (O2) tension. We herein demonstrated that metformin was highly cytotoxic under glucose-depleted, but not hypoxic (2% O2) conditions. In order to elucidate the underlying mechanisms of this selective cytotoxicity, we treated exposed DNA repair-deficient chicken DT40 cells with metformin under glucose-depleted conditions and measured cellular sensitivity...
2017: PloS One
https://www.readbyqxmd.com/read/28926170/efficacy-and-safety-of-saxagliptin-in-combination-with-metformin-as-initial-therapy-in-chinese-patients-with-type-2-diabetes-results-from-the-start-study-a-multicenter-randomized-double-blind-active-controlled-phase-3-trial
#9
Jingtao Dou, Jianhua Ma, Jun Liu, Changjiang Wang, Eva Johnsson, Hui Yao, June Zhao, Changyu Pan
OBJECTIVE: To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycemic control (HbA1c 8.0-12.0%). RESEARCH DESIGN AND METHODS: In this multicenter, double-blind, active-controlled study (The START study: NCT02273050), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo, or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/day over 8 weeks...
September 19, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28925645/vitamin-b12-deficiency-recognition-and-management
#10
Robert C Langan, Andrew J Goodbred
Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. Screening average-risk adults for vitamin B12 deficiency is not recommended. Screening may be warranted in patients with one or more risk factors, such as gastric or small intestine resections, inflammatory bowel disease, use of metformin for more than four months, use of proton pump inhibitors or histamine H2 blockers for more than 12 months, vegans or strict vegetarians, and adults older than 75 years...
September 15, 2017: American Family Physician
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#11
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markela Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923347/sulforaphane-improves-disrupted-er-mitochondria-interactions-and-suppresses-exaggerated-hepatic-glucose-production
#12
Emily Tubbs, Annika S Axelsson, Guillaume Vial, Claes B Wollheim, Jennifer Reuisset, Anders H Rosengren
AIMS: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs...
September 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28923291/use-of-prohibited-medication-a-potentially-overlooked-confounder-in-clinical-trials-omarigliptin-once-weekly-dpp-4-inhibitor-monotherapy-trial-in-18-to-45-year-olds
#13
Ira Gantz, Liubov Sokolova, Lokesh Jain, Carol Iredale, Edward A O'Neill, Ziwen Wei, Raymond Lam, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
PURPOSE: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. METHODS: Patients with T2DM who were ≥18 to <45 years of age and either drug-naive or not on an antihyperglycemic agent for ≥12 weeks with inadequate glycemic control were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 102) or placebo once weekly (n = 101) for 24 weeks...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28922161/comorbidity-analysis-between-alzheimer-s-disease-and-type-2-diabetes-mellitus-t2dm-based-on-shared-pathways-and-the-role-of-t2dm-drugs
#14
Reagon Karki, Alpha Tom Kodamullil, Martin Hofmann-Apitius
BACKGROUND: Various studies suggest a comorbid association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) indicating that there could be shared underlying pathophysiological mechanisms. OBJECTIVE: This study aims to systematically model relevant knowledge at the molecular level to find a mechanistic rationale explaining the existing comorbid association between AD and T2DM. METHOD: We have used a knowledge-based modeling approach to build two network models for AD and T2DM using Biological Expression Language (BEL), which is capable of capturing and representing causal and correlative relationships at both molecular and clinical levels from various knowledge resources...
September 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28921919/oral-glucose-lowering-with-linagliptin-and-metformin-compared-with-linagliptin-alone-as-initial-treatment-in-asian-patients-with-newly-diagnosed-type-2-diabetes-and-marked-hyperglycemia-subgroup-analysis-of-a-randomized-clinical-trial
#15
Ronald Cw Ma, Stefano Del Prato, Baptist Gallwitz, Vyankatesh K Shivane, Diane Lewis-D'Agostino, Zelie Bailes, Sanjay Patel, Jisoo Lee, Maximilian von Eynatten, Maximiliano Di Domenico, Stuart A Ross
AIMS/INTRODUCTION: Type 2 diabetes mellitus (T2DM) is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enrol predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed T2DM patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed T2DM patients with glycated hemoglobin A1c (HbA1c) 8...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28921862/efficacy-and-safety-of-the-addition-of-ertugliflozin-in-patients-with-type-2-diabetes-mellitus-inadequately-controlled-with-metformin-and-sitagliptin-the-vertis-sita2-placebo-controlled-randomized-study
#16
Samuel Dagogo-Jack, Jie Liu, Roy Eldor, Guillermo Amorin, Jeremy Johnson, Darcy Hille, Yuqin Liao, Susan Huyck, Gregory Golm, Steven G Terra, James P Mancuso, Samuel S Engel, Brett Lauring
AIMS: To assess ertugliflozin in patients with type 2 diabetes inadequately controlled on metformin and sitagliptin. MATERIALS AND METHODS: In this double-blind randomized study (NCT02036515), patients (glycated haemoglobin [HbA1c] 7.0-10.5% [53-91 mmol/mol] on metformin ≥1500 mg/day and sitagliptin 100 mg/day; estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m(2) ) were randomized to ertugliflozin 5 mg once-daily, 15 mg once-daily, or placebo. Primary efficacy endpoint was change from baseline in HbA1c at Week 26; treatment was continued until Week 52...
September 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28921708/scopoletin-supplementation-ameliorates-steatosis-and-inflammation-in-diabetic-mice
#17
Ra-Yeong Choi, Ju Ri Ham, Hae-In Lee, Hyun Wook Cho, Myung-Sook Choi, Seok-Kyu Park, Jin Lee, Myung-Joo Kim, Kwon-Il Seo, Mi-Kyung Lee
Scopoletin is a bioactive component in many edible plants and fruits. This study investigated the effects of scopoletin on hepatic steatosis and inflammation in a high-fat diet fed type 1 diabetic mice by comparison with metformin. Scopoletin (0.01%, w/w) or metformin (0.5%, w/w) was provided with a high-fat diet to streptozotocin-induced diabetic mice for 11 weeks. Both scopoletin and metformin lowered blood glucose and HbA1c , serum ALT, TNF-α and IL-6 levels, glucose intolerance, and hepatic lipid accumulation compared with the diabetic control group...
September 18, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28921513/use-of-a-clinical-laboratory-score-to-guide-treatment-of-gestational-diabetes
#18
Juliana B do Valle, Jean C Silva, Daniela S Oliveira, Lisiane Martins, Amanda Lewandowski, Wagner Horst
OBJECTIVE: To assess the outcomes of implementing a clinical-laboratory score in the treatment of pregnant women with gestational diabetes. METHODS: A retrospective before-and-after implementation analysis was undertaken using data and neonatal outcomes for pregnant women with gestational diabetes treated before (January 2011-December 2012; control group) and after (January 2013-December 2014; score group) introduction of a newly developed score. To evaluate the effects of score adoption, odds ratios with 95% confidence intervals were calculated after adjustment for confounding factors...
September 16, 2017: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/28919040/heme-binding-biguanides-target-cytochrome-p450-dependent-cancer-cell-mitochondria
#19
Zhijun Guo, Irina F Sevrioukova, Ilia G Denisov, Xia Zhang, Ting-Lan Chiu, Dafydd G Thomas, Eric A Hanse, Rebecca A D Cuellar, Yelena V Grinkova, Vanessa Wankhede Langenfeld, Daniel S Swedien, Justin D Stamschror, Juan Alvarez, Fernando Luna, Adela Galván, Young Kyung Bae, Julia D Wulfkuhle, Rosa I Gallagher, Emanuel F Petricoin, Beverly Norris, Craig M Flory, Robert J Schumacher, M Gerard O'Sullivan, Qing Cao, Haitao Chu, John D Lipscomb, William M Atkins, Kalpna Gupta, Ameeta Kelekar, Ian A Blair, Jorge H Capdevila, John R Falck, Stephen G Sligar, Thomas L Poulos, Gunda I Georg, Elizabeth Ambrose, David A Potter
The mechanisms by which cancer cell-intrinsic CYP monooxygenases promote tumor progression are largely unknown. CYP3A4 was unexpectedly associated with breast cancer mitochondria and synthesized arachidonic acid (AA)-derived epoxyeicosatrienoic acids (EETs), which promoted the electron transport chain/respiration and inhibited AMPKα. CYP3A4 knockdown activated AMPKα, promoted autophagy, and prevented mammary tumor formation. The diabetes drug metformin inhibited CYP3A4-mediated EET biosynthesis and depleted cancer cell-intrinsic EETs...
August 29, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28918830/metformin-has-positive-therapeutic-effects-in-colon-cancer-and-lung-cancer
#20
DeAnna Henderson, Danielle Frieson, Jeffrey Zuber, Solomon S Solomon
BACKGROUND: Metformin (MF), a diabetic drug, has antineoplastic activity as adjuvant therapy for breast cancer and prostate cancer. MF is thought to work via inhibition of mammalian target of rapamycin and activation of p53 and liver kinase B1 via adenosine 5'-monophosphate-activated protein kinase. We investigated survival, recurrences and metastasis in patients with type 2 diabetes mellitus (DM2) along with colorectal cancer (CC) or lung cancer (LC) taking MF using the electronic medical record in Memphis Veterans Affairs Medical Center (colon, n = 202; lung, n = 180)...
September 2017: American Journal of the Medical Sciences
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