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https://www.readbyqxmd.com/read/28324269/metformin-sensitizes-triple-negative-breast-cancer-to-proapoptotic-trail-receptor-agonists-by-suppressing-xiap-expression
#1
Elena Strekalova, Dmitry Malin, Harisha Rajanala, Vincent L Cryns
PURPOSE: Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. METHODS: Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28324038/efficacy-of-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-t2dm-patients-with-very-high-hba1c
#2
Muhammad Abdul-Ghani, Osama Mujahid, Ayman Mujahid, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
Aim: To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in poorly controlled type 2 diabetic patients with very high HbA1c (HbA1c>10%) on metformin plus sulfonylurea and long duration of disease. Research Design and Methods: 101 participants in Qatar Study with very poor glycemic control (HbA1c > 10%) and long duration of diabetes (10.9 years) on maximum/near-maximum doses of sulfonylurea plus metformin were randomized to receive: (i) pioglitazone plus weekly exenatide (Combination Therapy), or (ii) basal plus prandial insulin (Insulin Therapy) to maintain HbA1c <7...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#3
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFA) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323512/evaluating-the-costs-of-glycemic-response-with-canagliflozin-versus-dapagliflozin-and-empagliflozin-as-add-on-to-metformin-in-patients-with-type-2-diabetes-mellitus-in-the-united-arab-emirates
#4
Agata Schubert, Anders T Buchholt, Antoine C El Khoury, Ahmed Kamal, Vanessa Taieb
OBJECTIVE: This study evaluates the cost of achieving glycemic control with 3 sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE). METHODS: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014...
March 21, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28319830/anti-proliferative-effect-of-metformin-on-a-feline-injection-site-sarcoma-cell-line-independent-of-mtor-inhibition
#5
J Pierro, C Saba, K McLean, R Williams, E Karpuzoglu, R Prater, K Hoover, R Gogal
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8...
March 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28318105/metformin-as-add-on-to-intensive-insulin-therapy-in-type-1-diabetes-mellitus
#6
Frederik Staels, Carolien Moyson, Chantal Mathieu
We aimed to evaluate the effect of adjuvant metformin to intensive insulin therapy in patients with type 1 diabetes (T1DM). A 10 year retrospective study of 2 cohorts was performed. Cohort "MET" (n = 186) consisted of T1DM patients on adjuvant metformin for ≥ 6 months and cohort "CTR" (n = 62) consisted of T1DM patients who refused (n = 25) or adhered <6 months (n = 37) to metformin. HbA1c, BMI and daily insulin dose were registered yearly. A third cross-sectional group "REF" (n = 961) of T1DM patients not offered adjuvant metformin, was used as a reference for baseline comparison...
March 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28317873/a-new-method-to-evaluate-the-dose-effect-relationship-of-a-tcm-formula-gegen-qinlian-decoction-focus-mode-of-integrated-biomarkers
#7
Zhi-Qiang Huang, Xue-Mei Fan, Yi-Ming Wang, Qiong-Lin Liang, Xiao-Lin Tong, Yu Bai, Ying-Meng Li, Guo-An Luo, Chao Chen
It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28317764/cucurbitane-glycosides-from-the-fruit-of-siraitia-grosvenori-and-their-effects-on-glucose-uptake-in-human-hepg2-cells-in-vitro
#8
Fu Li, Fumei Yang, Xin Liu, Lun Wang, Bin Chen, Lianhong Li, Mingkui Wang
The mogrosides in the fruit of Siraitia grosvenori can serve as a sugar substitute for diabetics due to their sweetness, low calorie and positive effects on blood glucose level control. The present study was to purify the mogrosides from the fruit of S. grosvenori and evaluate their enhancement of glucose uptake rate in HepG2 cells in vitro. As a result, eighteen mogrosides were isolated, including six new ones and a known but new naturally occurring compound. The chemical structures of the new compounds were identified by 1D, 2D-NMR and HR-ESI-MS techniques, together with chemical methods...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28316081/the-antidiabetic-drug-metformin-decreases-mitochondrial-respiration-and-tricarboxylic-acid-cycle-activity-in-cultured-primary-rat-astrocytes
#9
Michaela C Hohnholt, Eva-Maria Blumrich, Helle S Waagepetersen, Ralf Dringen
Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping (13) C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-(13) C]glucose...
March 19, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28315697/the-role-of-the-tor-pathway-in-mediating-the-link-between-nutrition-and-longevity
#10
REVIEW
Oleh Lushchak, Olha Strilbytska, Veronika Piskovatska, Kenneth B Storey, Alexander Koliada, Alexander Vaiserman
The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging...
March 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#11
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28303721/effectiveness-and-safety-of-vildagliptin-and-vildagliptin-add-on-to-metformin-in-real-world-settings-in-egypt-results-from-the-guard-study
#12
Salah Shelbaya, Sameh Rakha
OBJECTIVE: The GUARD study evaluated the effectiveness, safety, and tolerability of vildagliptin treatment with or without metformin in patients with type 2 diabetes mellitus (T2DM) in real-life settings. Here we present the results of the GUARD study for the patient subset from Egypt. RESEARCH DESIGN AND METHODS: This was a 24 ± 6 weeks, prospective, non-interventional study that enrolled adult patients with T2DM receiving vildagliptin or vildagliptin + metformin combination therapy as per local prescribing information...
March 17, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#13
REVIEW
Dajun Zhao, Jian Yang, Lifang Yang
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28294366/antihyperalgesic-effects-of-indomethacin-ketorolac-and-metamizole-in-rats-effects-of-metformin
#14
Crystell Guadalupe Guzmán-Priego, Roberto Méndez-Mena, Manuel Alfonso Baños-González, Claudia Ivonne Araiza-Saldaña, Gabriela Castañeda-Corral, Jorge Elías Torres-López
Preclinical Research Metformin-dependent mechanisms have been implicated in the antinociceptive effect of some non-steroidal anti-inflammatory drugs (NSAIDs). In this study, the effect of local peripheral or systemic administration of metformin on the local peripheral or systemic antinociception induced by indomethacin, ketorolac and metamizole was assessed in the rat carrageenan-induced thermal hyperalgesia model. Rats were injected with carrageenan (1%, 50 µl) into the right hindpaw which reduced paw withdrawal latency, a measure of thermal hyperalgesia...
March 15, 2017: Drug Development Research
https://www.readbyqxmd.com/read/28292575/the-treatment-of-type-2-diabetes-mellitus-in-patients-with-chronic-kidney-disease-what-to-expect-from-new-oral-hypoglycemic-agents
#15
REVIEW
Luca Di Lullo, Michela Mangano, Claudio Ronco, Vincenzo Barbera, Antonio De Pascalis, Antonio Bellasi, Domenico Russo, Biagio Di Iorio, Mario Cozzolino
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), whose most common causes include hypertension, arteriosclerosis, and diabetes. About 40% of patients with diabetes develop CKD and intensive blood glucose control through pharmacological intervention can delay CKD progression. Standard therapies for the treatment of type 2 diabetes mellitus include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin. While these drugs have an important role in the management of type 2 diabetes, only the thiazolidinedione pioglitazone can be used across the spectrum of CKD (stages 2-5) and without dose adjustment...
March 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28285923/design-synthesis-and-structure-activity-relationship-studies-of-novel-free-fatty-acid-receptor-1-agonists-bearing-amide-linker
#16
Jianyong Yang, Zheng Li, Huilan Li, Chunxia Liu, Nasi Wang, Wei Shi, Chen Liao, Xingguang Cai, Wenlong Huang, Hai Qian
The free fatty acid receptor 1 (FFA1/GPR40) has attracted extensive attention as a novel antidiabetic target. Aiming to explore the chemical space of FFA1 agonists, a new series of lead compounds with amide linker were designed and synthesized by combining the scaffolds of NIH screened lead compound 1 and GW9508. Among them, the optimal lead compound 17 exhibited a considerable agonistic activity (45.78%) compared to the NIH screened compound 1 (15.32%). During OGTT in normal mice, the compound 17 revealed a significant glucose-lowering effect (-23...
March 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28284168/effects-of-postmeal-exercise-on-postprandial-glucose-excursions-in-people-with-type-2-diabetes-treated-with-add-on-hypoglycemic-agents
#17
Melissa L Erickson, Jonathan P Little, Jennifer L Gay, Kevin K McCully, Nathan T Jenkins
AIMS: Type 2 diabetes treatment primarily focuses on reducing hyperglycemia, including postprandial glucose excursions. Hypoglycemic agents are used clinically to lower fasting and postprandial glucose. Metformin is the first-line therapy; however, if metformin is inadequate then 'add-on' hypoglycemic agents are implemented. Postmeal exercise has been shown to lower postprandial glucose. The aim of this study was to assess if postmeal exercise provides additional glucose-lowering benefit, beyond medication alone, in those on add-on hypoglycemic agents...
March 8, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28283684/pharmacogenetics-in-type-2-diabetes-precision-medicine-or-discovery-tool
#18
REVIEW
Jose C Florez
In recent years, technological and analytical advances have led to an explosion in the discovery of genetic loci associated with type 2 diabetes. However, their ability to improve prediction of disease outcomes beyond standard clinical risk factors has been limited. On the other hand, genetic effects on drug response may be stronger than those commonly seen for disease incidence. Pharmacogenetic findings may aid in identifying new drug targets, elucidate pathophysiology, unravel disease heterogeneity, help prioritise specific genes in regions of genetic association, and contribute to personalised or precision treatment...
March 10, 2017: Diabetologia
https://www.readbyqxmd.com/read/28283393/effect-of-metformin-on-exercise-capacity-in-metabolic-syndrome
#19
Abi Albon Paul, Steven Aibor Dkhar, Sadishkumar Kamalanathan, Molly Mary Thabah, Melvin George, Indumathi Chandrasekaran, Vikneswaran Gunaseelan, Sandhiya Selvarajan
OBJECTIVE: Metabolic syndrome is a constellation of risk factors with increased predilection towards occurrence of cardiovascular diseases. Currently physical exercise and management with metformin are the prevailing treatment modalities for metabolic syndrome. Patients with metabolic syndrome have been found to have reduced exercise capacity over a period of time. Likewise metformin has been shown to decrease exercise capacity among healthy volunteers. Hence this study aims to evaluate the effect of metformin on the exercise capacity of patients with metabolic syndrome...
March 6, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28282557/the-effect-of-combined-photobiomodulation-and-metformin-on-open-skin-wound-healing-in-a-non-genetic-model-of-type-ii-diabetes
#20
Mohammadali Asghari, Ali Kanonisabet, Mandanad Safakhah, Zahra Azimzadeh, Ataroalsadat Mostafavinia, Abdollah Amini, Seyed Kamran Ghorishi, Reza JalaliFiroozkohi, Sahar Bayat, Mohammad Bayat
This study intended to examine the combined influences of photobiomodulation (PBM) and metformin on the microbial flora and biomechanical parameters of wounds in a non-genetic model of type II diabetes mellitus (TII DM). We induced a non-genetic model of TII DM in 20 rats by feeding them a 10% fructose solution for 2weeks followed by an injection of streptozotocin (STZ, 40mg/kg). After 21days from the injection of STZ, we induced one full-thickness skin wound in each of the diabetic rats. We randomly divided the rats into four groups: i) placebo; ii) pulsed wave laser (890nm, 80Hz, 0...
March 6, 2017: Journal of Photochemistry and Photobiology. B, Biology
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