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https://www.readbyqxmd.com/read/28344112/efficacy-and-safety-of-once-weekly-semaglutide-versus-once-daily-insulin-glargine-as-add-on-to-metformin-with-or-without-sulfonylureas-in-insulin-naive-patients-with-type-2-diabetes-sustain-4-a-randomised-open-label-parallel-group-multicentre-multinational
#1
Vanita R Aroda, Stephen C Bain, Bertrand Cariou, Milivoj Piletič, Ludger Rose, Mads Axelsen, Everton Rowe, J Hans DeVries
BACKGROUND: Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). METHODS: We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries...
March 23, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28337263/receptor-for-advanced-glycation-end-as-drug-targets-in-diabetes-induced-skin-lesion
#2
Xiang-Fang Chen, Wei Tang, Wei-Dong Lin, Zi-Yu Liu, Xiao-Xiao Lu, Bei Zhang, Fei Ye, Zhi-Min Liu, Jun-Jie Zou, Wan-Qing Liao
The involvement of the receptor for advanced glycation end (RAGE) in different diseases has been reviewed in great detail, previously, but the effects of diabetic drugs on RAGE-induced skin lesion during long course diabetes remains poorly understood. In the present study, we have shown that RAGE was overexpressed in both diabetic rats and human keratinocytes (HaCaT cells). Cell cycle arrest and apoptosis as well as alternations of relative protein levels were also found in diabetic rats and HaCaT cells with overexpression of RAGE that were rectified by metformin (Met) treatment...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28324049/piloting-a-remission-strategy-in-type-2-diabetes-results-of-a-randomized-controlled-trial
#3
Natalia McInnes, Ada Smith, Rose Otto, Jeffrey Vandermey, Zubin Punthakee, Diana Sherifali, Kumar Balasubramanian, Stephanie Hall, Hertzel C Gerstein
Context: Medical strategies targeting remission of type 2 diabetes have not been systematically studied. Objective: This trial assessed the feasibility, safety and potential to induce remission of a short-term intensive metabolic strategy. Design: A randomized, parallel, open-label pilot trial in 83 participants followed for 52 weeks. Setting: Ambulatory care. Participants: Patients with type 2 diabetes of up to 3 years in duration...
March 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322845/metformin-like-antidiabetic-cardio-protective-and-non-glycemic-effects-of-naringenin-molecular-and-pharmacological-insights
#4
REVIEW
Annah Nsoaki Nyane, Thabiso Bethwel Tlaila, Tanki Gabriel Malefane, Dudu Edith Ndwandwe, Peter Mark Oroma Owira
Metformin is a widely used drug for the treatment of type 2 diabetes (T2D). Its blood glucose-lowering effects are initially due to inhibition of hepatic glucose production and increased peripheral glucose utilization. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular complications in patients with diabetes. Adenosine Monophosphate Activated-Protein Kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism...
March 18, 2017: European Journal of Pharmacology
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/28315697/the-role-of-the-tor-pathway-in-mediating-the-link-between-nutrition-and-longevity
#6
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/28314484/impact-of-health-policy-and-practice-on-finding-the-best-fit-for-patients-with-type-2-diabetes-after-metformin-failure-croatian-pilot-study
#7
Maja Cigrovski Berković, Davorka Herman Mahečić, Marina Gradišer, Ines Bilić-Ćurčić
AIM: We assessed the impact of clinical practice and health policy on the choice and efficacy of different second-line therapies for the treatment of type 2 diabetes (T2DM) after failure of metformin. METHODS: This retrospective database analysis included 200 patients with a follow-up period of 6 months. The primary end-point was achievement of HbA1c <7% and fasting (FBG) and postprandial glucose levels (PPG) <7.2mmol/L and <10mmol/L, respectively after three and six months of different add-on treatments...
March 14, 2017: Primary Care Diabetes
https://www.readbyqxmd.com/read/28300022/optimization-of-a-modified-quechers-method-for-multiresidue-analysis-of-pharmaceuticals-and-personal-care-products-in-sewage-and-surface-water-by-lc-ms-ms
#8
Akanksha S Kachhawaha, Pranav M Nagarnaik, Manjusha Jadhav, Anjali Pudale Pawan K Labhasetwar, Kaushik Banerjee
A quick, sensitive multiresidue method was developed for the analysis of 19 multiclass pharmaceuticals and personal care products (PPCPs) in surface water and sewage water. The proposed modified QuEChERS method involved the extraction of water samples (10 mL) with acetonitrile (10 mL) after the addition of 1% acetic acid, 4 g magnesium sulfate, and 0.2 g ammonium acetate, and was validated in distilled water, surface water, and sewage water with respect to linearity, LOD and LOQ, precision, and accuracy. The LOD and LOQ varied within the ranges of 0...
March 16, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#9
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/28291580/restored-plasma-anandamide-and-endometrial-expression-of-fatty-acid-amide-hydrolase-in-women-with-polycystic-ovary-syndrome-by-the-combination-use-of-diane-35-and-metformin
#10
Na Cui, Xiaoye Feng, Zhiming Zhao, Jie Zhang, Yueming Xu, Luning Wang, Guimin Hao
PURPOSE: Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment. METHODS: Serum levels of anandamide and 2-arachidonoylglycerol andexpression of cannabinoid receptors and fatty acid amide hydrolase (FAAH) in the endometrium were compared between women with PCOS and infertile women without PCOS, as well as women with PCOS before and after treatment with Diane-35 and metformin...
March 10, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28285923/design-synthesis-and-structure-activity-relationship-studies-of-novel-free-fatty-acid-receptor-1-agonists-bearing-amide-linker
#11
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/28283684/pharmacogenetics-in-type-2-diabetes-precision-medicine-or-discovery-tool
#12
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/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#13
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
March 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28274796/dual-functional-lipomet-mediates-envelope-type-nanoparticles-to-combinational-oncogene-silencing-and-tumor-growth-inhibition
#14
Kai Shi, Yi Zhao, Lei Miao, Andrew Satterlee, Matthew Haynes, Cong Luo, Sara Musetti, Leaf Huang
The success of small interfering RNA (siRNA)-mediated gene silencing for cancer therapy is still limited because of its instability and poor intracellular internalization. Traditional cationic carriers cannot adequately meet the need for clinical application of siRNA. We herein report a dual-functional liposome containing a cholesterol derivative of metformin, i.e., LipoMET, which takes advantage of the fusogenic activity as well as intrinsic tumor apoptosis inducing ability of biguanide moiety to achieve a combinational anti-oncogenic effect...
March 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28274614/metformin-represses-glucose-starvation-induced-autophagic-response-in-microvascular-endothelial-cells-and-promotes-cell-death
#15
Samson Mathews Samuel, Suparna Ghosh, Yasser Majeed, Gnanapragasam Arunachalam, Mohamed M Emara, Hong Ding, Chris R Triggle
Metformin, the most frequently administered drug for the treatment of type 2 diabetes, is being investigated for its potential in the treatment of various types of cancer; however, the cellular basis for this putative anti-cancer action remains controversial. In the current study we examined the effect of metformin on endoplasmic reticulum (ER) stress and autophagy in glucose-starved micro-vascular endothelial cells (MECs). The rationale for our experimental protocol is that in a growing tumor MECs are subjected to hypoxia and nutrient/glucose starvation that results from the reduced supply and relatively high consumption of glucose...
March 6, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28273365/metformin-attenuates-renal-fibrosis-in-both-ampk%C3%AE-2-dependent-and-independent-manners
#16
Yenan Feng, Shuaixing Wang, Youyi Zhang, Han Xiao
Metformin is a well-known AMP-activated protein kinase (AMPK) activator, and it has been shown to inhibit organ fibrosis. Whether AMPKα2 mediates metformin protection against renal fibrosis remains unknown. Here, we aimed to investigate the role of the AMPKα2 isoform in mediating the inhibitory effect of metformin on renal fibrosis. Unilateral ureteral obstruction (UUO) was used to induce renal fibrosis in wild-type (WT) and AMPKα2 knockout (AMPKα2(-/-) ) mice. Metformin treatment was initiated 3 days before UUO and was continued until 7 days after UUO...
March 8, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28258677/metformin-its-potential-anti-cancer-and-anti-aging-effects
#17
Monika Podhorecka, Blanca Ibanez, Anna Dmoszyńska
The generally accepted mechanism of metformin's effect is stimulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). AMPK is directly activated by an increase in AMP:ATP ratio in metabolic stress conditions including hypoxia and glucose deprivation. Lately, many novel pathways, besides AMPK induction, have been revealed, which can explain some of metformin's beneficial effects. It may help to identify new targets for treatment of diabetes and metabolic syndrome. Moreover, metformin is now attracting the attention of researchers in fields other than diabetes, as it has been shown to have anti-cancer, immunoregulatory and anti-aging effects...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28250276/atractylenolide-iii-enhances-energy-metabolism-by-increasing-the-sirt-1-and-pgc1%C3%AE-expression-with-ampk-phosphorylation-in-c2c12-mouse-skeletal-muscle-cells
#18
Mi Young Song, Hyo Won Jung, Seok Yong Kang, Yong-Ki Park
Targeting energy expenditure provides a potential alternative strategy for achieving energy balance to combat obesity and the development of type 2 diabetes mellitus (T2DM). In the present study, we investigated whether atractylenolide III (AIII) regulates energy metabolism in skeletal muscle cells. Differentiated C2C12 myotubes were treated with AIII (10, 20, or 50 µM) or metformin (2.5 mM) for indicated times. The levels of glucose uptake, the expressions of key mitochondrial biogenesis-related factors and their target genes were measured in C2C12 myotubes...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28249192/occurrence-of-pharmaceuticals-and-personal-care-products-in-effluent-dominated-saudi-arabian-coastal-waters-of-the-red-sea
#19
Aasim M Ali, Helene Thorsen Rønning, Walied Alarif, Roland Kallenborn, Sultan S Al-Lihaibi
The occurrence of selected pharmaceuticals and personal care products (PPCPs) and the pesticide atrazine were investigated in seawater samples collected from stations located at effluent dominated sites in the Saudi Arabian coastal waters of the Red Sea. PPCPs were analysed using solid phase extraction (SPE) followed by high performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). A multi component method for the ultra-trace level quantification of 13 target PPCPs in Seawater was developed and validated for the here performed study...
May 2017: Chemosphere
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#20
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
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