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https://www.readbyqxmd.com/read/29352482/influence-of-pharmacogenetic-polymorphisms-and-demographic-variables-on-metformin-pharmacokinetics-in-an-admixed-brazilian-cohort
#1
Ana Beatriz Santoro, Mariana Rodrigues Botton, Claudio José Struchiner, Guilherme Suarez-Kurtz
AIM: To identify pharmacogenetic and demographic variables that influence the systemic exposure to metformin in an admixed Brazilian cohort. METHODS: The extreme discordant phenotype was used to select 106 data sets from nine metformin bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor SP1 were genotyped and a validated panel of ancestry informative markers was used to estimate the individual proportions of biogeographical ancestry...
January 20, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29351716/effect-of-metformin-on-glycemic-control-in-patients-with-type-1-diabetes-a-meta-analysis-of-randomized-controlled-trials
#2
Haiyang Meng, Ailing Zhang, Yan Liang, Jie Hao, Xiaojian Zhang, Jingli Lu
BACKGROUND: For T1D patients, adding metformin to insulin therapies is thought to improve blood glucose levels, but current evidence does not support this clinical benefit. Additional data from large clinical trials are now available; therefore, we conducted a meta-analysis of studies on assessing the efficacy and adverse effects of metformin. METHODS: We searched the MEDLINE, EMBASE and Cochrane Library databases for data from randomized controlled trials (RCTs)...
January 19, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29351188/proangiogenic-effect-of-metformin-in-endothelial-cells-is-via-upregulation-of-vegfr1-2-and-their-signaling-under-hyperglycemia-hypoxia
#3
Sherin Bakhashab, Farid Ahmed, Hans-Juergen Schulten, Fahad W Ahmed, Michael Glanville, Mohammed H Al-Qahtani, Jolanta U Weaver
Cardiovascular disease is the leading cause of morbidity/mortality worldwide. Metformin is the first therapy offering cardioprotection in type 2 diabetes and non-diabetic animals with unknown mechanism. We have shown that metformin improves angiogenesis via affecting expression of growth factors/angiogenic inhibitors in CD34⁺ cells under hyperglycemia-hypoxia. Now we studied the direct effect of physiological dose of metformin on human umbilical vein endothelial cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia...
January 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29350661/retrospective-analysis-of-the-effects-of-a-highly-standardized-mixture-of-berberis-aristata-silybum-marianum-and-monacolins-k-and-ka-in-diabetic-patients-with-dyslipidemia
#4
Francesco Di Pierro, Pietro Putignano, Nicola Villanova
BACKGROUND: Berberine, an alkaloid with both glucose- and cholesterol-lowering action, is also characterized by an anti-diarrheal effect. Consequently, berberine-based therapies are recommended for diabetic patients with irritable bowel syndrome (IBS) or gut discomfort caused by metformin. AIM: As the anti-glycemic and cholesterol-lowering action of berberine is improved by co-administration with P-glycoprotein inhibitors and naturally derived statins, we have analyzed the effect of the food supplement Berberol®K (hereafter referred to as BSM) containing, berberine, silymarin, and a highly standardized red yeast rice containing monacolins K and KA in the ratio 1:1 but no secondary monacolins, dehydromonacolins, or citrinin (Monakopure™-K20)...
January 16, 2018: Acta Bio-medica: Atenei Parmensis
https://www.readbyqxmd.com/read/29348889/metformin-and-temozolomide-a-synergic-option-to-overcome-resistance-in-glioblastoma-multiforme-models
#5
Silvia Valtorta, Alessia Lo Dico, Isabella Raccagni, Daniela Gaglio, Sara Belloli, Letterio S Politi, Cristina Martelli, Cecilia Diceglie, Marcella Bonanomi, Giulia Ercoli, Valentina Vaira, Luisa Ottobrini, Rosa Maria Moresco
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with poor survival. Cytoreduction in association with radiotherapy and temozolomide (TMZ) is the standard therapy, but response is heterogeneous and life expectancy is limited. The combined use of chemotherapeutic agents with drugs targeting cell metabolism is becoming an interesting therapeutic option for cancer treatment. Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell line (U251) and overcomes TMZ-resistance in T98G GBM cell line...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348175/glucose-regulates-mafa-transcription-factor-abundance-and-insulin-gene-expression-by-inhibiting-amp-activated-protein-kinase-in-pancreatic-%C3%AE-cells
#6
Ryo Iwaoka, Kohsuke Kataoka
Insulin mRNA expression in pancreatic islet β-cells is upregulated by extracellular glucose concentration, but the underlying mechanism remains incompletely understood. MafA is a transcriptional activator specifically enriched in β-cells that binds to the insulin gene promoter. Its expression is transcriptionally and post-transcriptionally regulated by glucose. Moreover, AMP-activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is inhibited by high glucose, and this inhibition is essential for the up-regulation of insulin gene expression and glucose-stimulated insulin secretion (GSIS)...
January 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29348086/pharmaceutical-equivalent-dissertation-of-metformin-hydrochloride-brands
#7
Safila Naveed, Huma Dilshad, Maheen Nafees, Muhammad Ibrar Shinwari, Khan Usmanghani, Ghulam Sarwar
The aim of study is to establish pharmaceutical equivalence of different brands of Metformin tablets available in Karachi, Pakistan. The quality control parameters which are studied are weight variation test, hardness test, thickness, friability, disintegration and dissolution specified by BP/USP (British and United State Pharmacopoeia). Weight variation and hardness value requirement was complied by all brands. Disintegration time for all brands was within range i.e. 15 minutes and also complies with the BP/USP recommendation...
January 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29345910/qualitative-and-quantitative-analysis-of-ethanolic-extract-and-phenolic-fraction-of-jatropha-aethiopica-euphorbiaceae-leaves-and-their-hypoglycemic-potential
#8
Daylin Gamiotea-Turro, Nathalia Aparecida de Paula Camaforte, Alexander Barbaro Valerino-Diaz, Yarelis Ortiz Nunez, Daniel Rinaldo, Anne Ligia Dokkedal, José Roberto Bosqueiro, Lourdes Campaner Dos Santos
While Jatropha aethiopica, popularly known in Cuba as "mata diabetes", is used in salads and as a dietary supplement, its chemical composition and antidiabetic properties yet remains unclear. In this work, we evaluate the qualitative and quantitative composition of ethanolic extract (EE) and phenolic fraction (PF) of Jatropha aethiopica, leaves and their hypoglycemic and hypolipidemic activity. Chemical fractionation of the ethanolic extract yielded nine compounds, which included protocatechuic acid (1), chlorogenic acid (2), caffeic acid (3), quercetin 3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranolsyl-(1→6)]-β-D-galactopyranoside (4), a new kaempferol 3-O-α-L-rhamnopyranosyl-(1→4)-[α-L-rhamnopyranolsyl-(1→6)]-β-D-galactopyranoside (5), kaempferol 3-O-α-L-rhamnopyranosyl-(1→2[α-L-rhamnopyranolsyl-(1→6)]-β-D-glucopyranoside (6), rutin (7), kaempferol 3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (8) and quercetin (9)...
January 18, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29345505/the-pharmacological-management-of-metabolic-syndrome
#9
Julie Rask Larsen, Lorena Dima, Christoph U Correll, Peter Manu
Introduction The metabolic syndrome includes a constellation of several well-established risk factors, which need to be aggressively treated in order to prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines for the treatment of individual components of the metabolic syndrome focus on cardiovascular benefits as resulted from clinical trials, specific recent recommendations on the pharmacological management of metabolic syndrome are lacking. The objective of present paper was to review the therapeutic options for metabolic syndrome and its components, the available evidence related to their cardiovascular benefits, and to evaluate the extent to which they should influence the guidelines for clinical practice...
January 18, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29344438/new-therapeutic-approaches-in-obesity-and-metabolic-syndrome-associated-with-polycystic-ovary-syndrome
#10
REVIEW
Fatima Saleem, Syed W Rizvi
Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting reproductive and metabolic indices. PCOS is commonly associated with a high prevalence of insulin resistance and obesity; this association carries an increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. Guidelines recommend lifestyle modification, metformin, hormonal contraceptives (HCs), and bariatric surgery as the main treatment options in obese patients with PCOS. Studies are being conducted to test the efficacy of existing treatment options as well as to discover new therapies...
November 13, 2017: Curēus
https://www.readbyqxmd.com/read/29344336/treating-nonalcoholic-fatty-liver-disease-in-patients-with-type-2-diabetes-mellitus-a-review-of-efficacy-and-safety
#11
REVIEW
Elizabeth P Mills, K Paige D Brown, Jennifer D Smith, Phillip W Vang, Katie Trotta
Objective: To review current literature for the efficacy and safety of treatment for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Data sources: A PubMed literature search from January 1990 to June 2017 was conducted using the search terms nonalcoholic fatty liver disease, diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin...
January 2018: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29344225/metformin-enhances-the-chemosensitivity-of-hepatocarcinoma-cells-to-cisplatin-through-ampk-pathway
#12
Hao Dong, Jungang Huang, Kang Zheng, Dong Tan, Qi Chang, Genqiang Gong, Qing Zhang, Hanqiu Tang, Jianguo Sun, Shaoyu Zhang
This study investigated the effect of metformin on chemosensitivity of hepatocarcinoma cells to cisplatin and the possible mechanism. HepG2 and Huh-7 hepatoma cells were treated with cisplatin at concentrations of 0, 2, 4, 6, 8 and 10 µM for 48 h. Proliferation of HepG2 and Huh-7 hepatoma cells were detected by MTT assay. Apoptosis of hepatocellular carcinoma cells was detected by flow cytometry. Western blot analysis was used to detect the expression of 5-monophosphate-activated protein kinase (AMPK) and p-AMPK protein...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344202/metformin-in-combination-with-cisplatin-inhibits-cell-viability-and-induces-apoptosis-of-human-ovarian-cancer-cells-by-inactivating-erk-1-2
#13
Jian-Hong Dang, Zhi-Jun Jin, Xiao-Jun Liu, Dian Hu, Jing Wang, Yan Luo, Ling-Ling Li
Metformin protects against insulin resistance by restoring insulin sensitivity and may also possess anticancer activity. The aim of the present study was to investigate the effects of metformin alone or combined with cisplatin (DDP) on the cell viability and apoptosis of HO-8910 human ovarian cancer cells, and to investigate metformin as a potential novel therapeutic for treating ovarian cancer. The viability of HO-8910 cells was assessed using a cell proliferation and cytotoxicity assay following treatment with different concentrations of metformin (0...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343628/keeping-the-home-fires-burning-amp-activated-protein-kinase
#14
REVIEW
D Grahame Hardie
Living cells obtain energy either by oxidizing reduced compounds of organic or mineral origin or by absorbing light. Whichever energy source is used, some of the energy released is conserved by converting adenosine diphosphate (ADP) to adenosine triphosphate (ATP), which are analogous to the chemicals in a rechargeable battery. The energy released by the conversion of ATP back to ADP is used to drive most energy-requiring processes, including cell growth, cell division, communication and movement. It is clearly essential to life that the production and consumption of ATP are always maintained in balance, and the AMP-activated protein kinase (AMPK) is one of the key cellular regulatory systems that ensures this...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29343420/ampk-re-activation-suppresses-hepatic-steatosis-but-its-downregulation-does-not-promote-fatty-liver-development
#15
Nadia Boudaba, Allison Marion, Camille Huet, Rémi Pierre, Benoit Viollet, Marc Foretz
Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism...
January 9, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29342230/metformin-as-an-anti-cancer-agent-actions-and-mechanisms-targeting-cancer-stem-cells
#16
Nipun Saini, Xiaohe Yang
Metformin, a first line medication for type II diabetes, initially entered the spotlight as a promising anti-cancer agent due to epidemiologic reports that found reduced cancer risk and improved clinical outcomes in diabetic patients taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical studies determined that metformin impairs cellular metabolism and suppresses oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and mTOR pathways. Recently, the anti-cancer potential of metformin has gained increasing interest due to its inhibitory effects on cancer stem cells (CSCs), which are associated with tumor metastasis, drug resistance, and relapse...
October 7, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29342199/a-non-linear-pharmacokinetic-pharmacodynamic-relationship-of-metformin-in-healthy-volunteers-an-open-label-parallel-group-randomized-clinical-study
#17
Hyewon Chung, Jaeseong Oh, Seo Hyun Yoon, Kyung-Sang Yu, Joo-Youn Cho, Jae-Yong Chung
BACKGROUND: The aim of this study was to explore the pharmacokinetic-pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the administration of 250 mg and 1000 mg of metformin in healthy volunteers. METHODS: A total of 20 healthy male volunteers were randomized to receive two doses of either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by 1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was assessed using oral glucose tolerance tests before and after metformin administration...
2018: PloS One
https://www.readbyqxmd.com/read/29341443/stachyose-improves-inflammation-through-modulating-gut-microbiota-of-high-fat-diet-streptozotocin-induced-type-2-diabetes-in-rats
#18
Guimei Liu, Jia Bei, Li Liang, Guoyong Yu, Lu Li, Quanhong Li
SCOPE: The present study was undertaken to assess the effects of stachyose (STS) on type 2 diabetes in rats, and changes in the gut microbiota compared to metformin (MET). METHODS AND RESULTS: The type 2 diabetic model was successfully established via a high-fat diet (HFD) / streptozotocin (STZ) in Wistar rats, and STS or MET was administered for 4 weeks. Blood was collected to analyze biochemical parameters, pancreas for mRNA expression of related gene and contents of colon for gut microbiota...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29340159/recurrent-lactic-acidosis-and-hypoglycemia-with-inadvertent-metformin-use-a-case-of-look-alike-pills
#19
Tess Jacob, Renee Garrick, Michael D Goldberg
Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#20
Jianjun Han, Weiya Z Wysham, Yan Zhong, Hui Guo, Lu Zhang, Kim M Malloy, Hallum K Dickens, Gene Huh, Douglas Lee, Liza Makowski, Chunxiao Zhou, Victoria L Bae-Jump
Obesity is a significant risk factor for ovarian cancer (OC) and associated with worse outcomes for this disease. We assessed the anti-tumorigenic effects of metformin in human OC cell lines and a genetically engineered mouse model of high grade serous OC under obese and lean conditions. Metformin potently inhibited growth in a dose-dependent manner in all four human OC cell lines through AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of apoptosis, reduction of invasion and decreased hTERT expression...
December 19, 2017: Oncotarget
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