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https://www.readbyqxmd.com/read/28938439/single-dose-metformin-enhances-bile-acid-induced-glp-1-secretion-in-patients-with-type-2-diabetes
#1
Andreas Brønden, Anders Albér, Ulrich Rohde, Jens F Rehfeld, Jens J Holst, Tina Vilsbøll, Filip K Knop
Context: Despite a position as the first-line pharmacotherapy in type 2 diabetes, the glucose-lowering mechanisms of metformin remain to be fully clarified. Gut-derived modes of action, including suppression of bile acid reabsorption and a resulting increase in GLP-1 secretion, has been proposed. Objective: The aim of this study was to assess the GLP-1 secretory and gluco-metabolic effects of endogenously released bile, with and without concomitant single-dose administration of metformin in patients with type 2 diabetes...
August 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938433/type-2-diabetes-and-osteoporosis-a-guide-to-optimal-management
#2
Stavroula Paschou, Anastasia D Dede, Panagiotis G Anagnostis, Andromachi Vryonidou, Daniel Morganstein, Dimitrios G Goulis
Context: Both type 2 diabetes (T2D) and osteoporosis are affected by aging and quite often co-exist. Furthermore, the fracture risk in patients with T2D is increased. The aim of this article is to review updated information on osteoporosis and fracture risk in patients with T2D, to discuss the effects of diabetes treatment on bone metabolism, as well as the effect of anti-osteoporotic medications on the incidence and control of T2D and to provide a personalized guide to the optimal management...
June 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28937612/houttuynia-cordata-facilitates-metformin-on-ameliorating-insulin-resistance-associated-with-gut-microbiota-alteration-in-oletf-rats
#3
Jing-Hua Wang, Shambhunath Bose, Soo-Kyoung Lim, AbuZar Ansari, Young-Won Chin, Han Seok Choi, Hojun Kim
Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone...
September 22, 2017: Genes
https://www.readbyqxmd.com/read/28936623/acute-renal-metabolic-effect-of-metformin-assessed-with-hyperpolarised-mri-in-rats
#4
Haiyun Qi, Per M Nielsen, Marie Schroeder, Lotte B Bertelsen, Fredrik Palm, Christoffer Laustsen
AIMS/HYPOTHESIS: Metformin inhibits hepatic mitochondrial glycerol phosphate dehydrogenase, thereby increasing cytosolic lactate and suppressing gluconeogenesis flux in the liver. This inhibition alters cytosolic and mitochondrial reduction-oxidation (redox) potential, which has been reported to protect organ function in several disease states including diabetes. In this study, we investigated the acute metabolic and functional changes induced by metformin in the kidneys of both healthy and insulinopenic Wistar rats used as a model of diabetes...
September 21, 2017: Diabetologia
https://www.readbyqxmd.com/read/28936150/prevalence-of-poor-glycemic-and-blood-pressure-control-and-pattern-of-drug-use-among-primary-health-care-outpatients-in-al-ahsa-saudi-arabia
#5
Promise M Emeka, Ahmed Al Mukalaf, Hussien Al Helal, Tahir M Khan, Mishial A Almukalf
OBJECTIVES: To assess drug use pattern and the effect on glycemic and blood pressure (BP) control in type 2 diabetes mellitus (T2DM) and hypertensive patients. Furthermore, to evaluate the duration of drug use and antecedence in diagnosis. METHODOLOGY: A cross-sectional study design, comprising interview/questionnaire targeting outpatients attending primary health centers in Al Ahsa was adopted. During the interview, their fasting blood glucose, weight, and height were measured, along with their BP...
July 2017: International Journal of Health Sciences
https://www.readbyqxmd.com/read/28935544/metformin-improves-obesity-associated-inflammation-by-altering-macrophages-polarization
#6
Yuanyuan Jing, Fan Wu, Dai Li, Lei Yang, Qi Li, Rong Li
Obesity is reported to be a chronic low-grade inflammatory state. Adipose tissue macrophages play a key role in obesity-related inflammation. Metformin, the most widely used anti-diabetic drug, has recently been reported to have an effect on inflammation, but the mechanism is poorly understood. This study aims to investigate how metformin works on chronic low-grade inflammation in obesity and whether the mechanism underlying it is associated with macrophage polarization. Metformin was administered for 7 weeks to high fat-fed C57/6J male mice in vivo...
September 18, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28933769/a-lanosteryl-triterpene-from-protorhus-longifolia-improves-glucose-tolerance-and-pancreatic-beta-cell-ultrastructure-in-type-2-diabetic-rats
#7
Sihle E Mabhida, Rebamang A Mosa, Dambudzo Penduka, Foluso O Osunsanmi, Phiwayinkosi V Dludla, Tryana G Djarova, Andy R Opoku
Type 2 diabetes remains one of the leading causes of death worldwide. Persistent hyperglycemia within a diabetic state is implicated in the generation of oxidative stress and aggravated inflammation that is responsible for accelerated modification of pancreatic beta cell structure. Here we investigated whether a lanosteryl triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), isolated from Protorhus longifolia can improve glucose tolerance and pancreatic beta cell ultrastructure by reducing oxidative stress and inflammation in high fat diet and streptozotocin-induced type 2 diabetes in rats...
July 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28933290/nutraceuticals-and-repurposed-drugs-of-phytochemical-origin-in-prevention-and-interception-of-chronic-degenerative-disease-and-cancer
#8
Adriana Albini, Barbara Bassani, Denisa Baci, Katiuscia Dallaglio, Matteo Gallazzi, Paola Corradino, Antonino Bruno, Douglas M Noonan
Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For many of these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy, thus the validation of novel (chemo)preventive and interceptive approaches, of new or repurposed agents, alone or in combination with registered drugs, are urgently required. Phytochemicals (triterpenoids, flavonoids, retinoids) and their derivatives, non-steroidal anti-inflammatory drugs (aspirin) as well as biguanides (metformin and phenformin) originally developed from phytochemical backbones, are multi-target agents showing anti-angiogenic and anti-anti-inflammatory proprieties...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28932995/pharmacokinetics-and-preliminary-pharmacodynamics-of-single-and-multiple-dose-lyophilized-recombinant-glucagon-like-peptide-1-receptor-agonist-re-4-in-chinese-patients-with-type-2-diabetes-mellitus
#9
Yitong Wang, Bingfeng Xu, Lixia Zhu, Kun Lou, Yingli Chen, Xia Zhao, Qian Wang, Ling Xu, Xiaohui Guo, Linong Ji, Yimin Cui, Yi Fang
BACKGROUND AND OBJECTIVES: Recombinant glucagon-like peptide-1 receptor agonist (rE-4) is a glucagon-like peptide-1 receptor agonist, which has the same amino acid sequence to exenatide, except for the C-terminal deamidated. This study assessed the pharmacokinetics and preliminary pharmacodynamics of rE-4, following single and multiple subcutaneous injections in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN AND METHODS: In the randomized, open-label study, Chinese patients with T2DM (n = 36) were randomly assigned to three groups of rE-4 (n = 12), rE-4 with metformin (n = 12) and exenatide (n = 12, as the control group) for 12 weeks...
September 20, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28932240/perspectives-on-peripheral-neuropathy-as-a-consequence-of-metformin-induced-vitamin-b12-deficiency-in-t2dm
#10
REVIEW
Marwan A Ahmed, George L Muntingh, Paul Rheeder
Peripheral neuropathy (PN) is a primary complication of type 2 diabetes mellitus (T2DM) and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28931178/the-oral-dipeptidyl-peptidase-4-inhibitor-sitagliptin-increases-circulating-levels-of-stromal-derived-factor-1-alpha
#11
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
#12
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/28927780/effects-of-metformin-on-proliferation-and-apoptosis-of-human-megakaryoblastic-dami-and-meg-01-cells
#13
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
#14
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/28925645/vitamin-b12-deficiency-recognition-and-management
#15
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
#16
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
#17
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
#18
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
#19
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/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
#20
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
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