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Metformin AND AMPK

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https://www.readbyqxmd.com/read/28427181/metformin-inhibits-alk1-mediated-angiogenesis-via-activation-of-ampk
#1
Ying Ying, Takashi Ueta, Shanshan Jiang, Hui Lin, Yuanyuan Wang, Demetrios Vavvas, Rong Wen, Ye-Guang Chen, Zhijun Luo
Anti-VEGF therapy has been proven to be effective in the treatment of pathological angiogenesis. However, therapy resistance often occurs, leading to development of alternative approaches. The present study examines if AMPK negatively regulates ALK1-mediated signaling events and associated angiogenesis. Thus, we treated human umbilical vein endothelial cells with metformin as well as other pharmacological AMPK activators and showed that activation of AMPK inhibited Smad1/5 phosphorylation and tube formation induced by BMP9...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423712/model-based-unsupervised-learning-informs-metformin-induced-cell-migration-inhibition-through-an-ampk-independent-mechanism-in-breast-cancer
#2
Arjun P Athreya, Krishna R Kalari, Junmei Cairns, Alan J Gaglio, Quin F Wills, Nifang Niu, Richard Weinshilboum, Ravishankar K Iyer, Liewei Wang
We demonstrate that model-based unsupervised learning can uniquely discriminate single-cell subpopulations by their gene expression distributions, which in turn allow us to identify specific genes for focused functional studies. This method was applied to MDA-MB-231 breast cancer cells treated with the antidiabetic drug metformin, which is being repurposed for treatment of triple-negative breast cancer. Unsupervised learning identified a cluster of metformin-treated cells characterized by a significant suppression of 230 genes (p-value < 2E-16)...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410530/metformin-attenuated-endotoxin-induced-acute-myocarditis-via-activating-ampk
#3
Gang Liu, Kejia Wu, Li Zhang, Jie Dai, Wei Huang, Ling Lin, Pu Ge, Fuling Luo, Han Lei
Metformin is a widely used anti-diabetic drug and increasing evidence suggests that metformin have profound cardioprotective effects under both diabetic and non-diabetic situations. The protective benefits of metformin have been proved in diabetic patients with cardiovascular complications and in experimental animals with myocardial infarction and cardiac hypertrophy. In the present study, we found that treatment with metformin inhibited the cardiac expression of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 6 (IL-6) in endotoxin-challenged mice...
April 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28393693/update-on-the-protective-renal-effects-of-metformin-in-diabetic-nephropathy
#4
Andreas Eisenreich, Ulrike Leppert
BACKGROUND: Diabetic nephropathy is one of the most important complications in patients with diabetes mellitus. Main steps crucial for the pathogenesis of diabetic nephropathy involve amongst others the modulation of cell signaling via AMP-activated kinase (AMPK) and mammalian target of rapamycin (mTOR), reactive oxygen generation, and endoplasmic reticulum stress under diabetic or hyperglycemic conditions. These processes mediate increased loss of renal cells, such as podocytes, which consequentially leads to renal damage and loss of renal functions, such as structural integrity and glomerular filtration in diabetic nephropathy...
April 4, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28384260/denv-up-regulates-the-hmg-coa-reductase-activity-through-the-impairment-of-ampk-phosphorylation-a-potential-antiviral-target
#5
Rubén Soto-Acosta, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Antonio H Angel-Ambrocio, Rosa M Del Angel
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28382202/mitochondria-targeted-metformins-anti-tumour-and-redox-signalling-mechanisms
#6
REVIEW
Balaraman Kalyanaraman, Gang Cheng, Micael Hardy, Olivier Ouari, Adam Sikora, Jacek Zielonka, Michael Dwinell
Reports suggest that metformin exerts anti-cancer effects in diabetic individuals with pancreatic cancer. Thus, metformin is currently being repurposed as a potential drug in cancer treatment. Studies indicate that potent metformin analogues are required in cancer treatment because of the low bioavailability of metformin in humans at conventional antidiabetic doses. We proposed that improved mitochondrial targeting of metformin by attaching a positively charged lipophilic triphenylphosphonium group will result in a new class of mitochondria-targeted metformin analogues with significantly enhanced anti-tumour potential...
April 6, 2017: Interface Focus
https://www.readbyqxmd.com/read/28380462/metformin-inhibits-proliferation-and-growth-hormone-secretion-of-gh3-pituitary-adenoma-cells
#7
Jiayin An, Xiangdong Pei, Zhenle Zang, Zheng Zhou, Jintao Hu, Xin Zheng, Yin Zhang, Jiaojiang He, Lian Duan, Rufei Shen, Weihua Zhang, Feng Zhu, Song Li, Hui Yang
Metformin is an anti-hyperglycemic agent used to treat diabetes, and recent evidence suggests it has antitumor efficacy. Because growth hormone-secreting pituitary adenoma (GH-PA) patients have a high incidence of diabetes frequently treated with metformin, we assessed the antitumor effect of metformin on GH-PA. We found that metformin effectively inhibited proliferation and induced apoptosis in the GH-PA cell line GH3. We detected a decrease in mitochondrial membrane potential (MMP), an increase in expression of pro-apoptotic proteins, and a decrease in expression of an anti-apoptotic protein in metformin-treated GH3 cells, which suggests involvement of the mitochondrial-mediated apoptosis pathway...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28373018/corrigendum-to-metformin-has-adenosine-monophosphate-activated-protein-kinase-ampk-independent-effects-on-lps-stimulated-rat-primary-microglial-cultures-pharmacol-rep-62-2010-827-848
#8
Krzysztof Łabuzek, Sebastian Liber, Bożena Gabryel, Bogusław Okopień
No abstract text is available yet for this article.
March 31, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28364040/hypoxia-reduces-hnf4%C3%AE-mody1-protein-expression-in-pancreatic-%C3%AE-cells-by-activating-amp-activated-protein-kinase
#9
Yoshifumi Sato, Tomonori Tsuyama, Chinami Sato, Md Fazlul Karim, Tatsuya Yoshizawa, Masahiro Inoue, Kazuya Yamagata
Hypoxia plays a role in the deterioration of β-cell function. Hepatocyte nuclear factor 4α (HNF4α) has an important role in pancreatic β-cells, and mutations of the human HNF4A gene cause a type of maturity-onset diabetes of the young (MODY1). However, it remains unclear whether hypoxia affects the expression of HNF4α in β-cells. Here, we report that hypoxia reduces HNF4α protein expression in β-cells. Hypoxia-inducible factor (HIF) was not involved in the down-regulation of HNF4α under hypoxic conditions...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28363500/corrigendum-to-metformin-affects-macrophages-phenotype-and-improves-the-activity-of-glutathione-peroxidase-superoxide-dismutase-catalase-and-decreases-malondialdehyde-concentration-in-a-partially-ampk-independent-manner-in-lps-stimulated-human-monocytes-macrophages
#10
Łukasz Bułdak, Krzysztof Łabuzek, Rafał Jakub Bułdak, Michał Kozłowski, Grzegorz Machnik, Sebastian Liber, Dariusz Suchy, Anna Duława-Bułdak, Bogusław Okopień
No abstract text is available yet for this article.
March 28, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28356082/anti-tumor-effects-of-everolimus-and-metformin-are-complementary-and-glucose-dependent-in-breast-cancer-cells
#11
Gerke Ariaans, Mathilde Jalving, Emma Geertruida Elisabeth de Vries, Steven de Jong
BACKGROUND: Clinical efficacy of the mTOR inhibitor everolimus is limited in breast cancer and regularly leads to side-effects including hyperglycemia. The AMPK inhibitor and anti-diabetic drug metformin may counteract everolimus-induced hyperglycemia, as well as enhancing anti-cancer efficacy. We investigated the glucose-dependent growth-inhibitory properties of everolimus, metformin and the combination in breast cancer cell lines. METHODS: The breast cancer cell lines MCF-7, MDA-MB-231 and T47D were cultured in media containing 11 mM or 2...
March 29, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28351720/estradiol-effects-on-hypothalamic-ampk-and-bat-thermogenesis-a-gateway-for-obesity-treatment
#12
REVIEW
Miguel López, Manuel Tena-Sempere
In addition to their prominent roles in the control of reproduction, estrogens are important modulators of energy balance, as evident in conditions of deficiency of estrogens, which are characterized by increased feeding and decreased energy expenditure, leading to obesity. AMP-activated protein kinase (AMPK) is a ubiquitous cellular energy gauge that is activated under conditions of low energy, increasing energy production and reducing energy wasting. Centrally, the AMPK pathway is a canonical route regulating energy homeostasis, by integrating peripheral signals, such as hormones and metabolites, with neuronal networks...
March 25, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28339020/metformin-inhibits-endothelial-progenitor-cell-migration-by-decreasing-matrix-metalloproteinases-mmp-2-and-mmp-9-via-the-ampk-mtor-autophagy-pathway
#13
Wen-Dong Li, Neng-Ping Li, Dan-Dan Song, Jian-Jie Rong, Ai-Min Qian, Xiao-Qiang Li
The aim of the present study was to investigate the effect of metformin on endothelial progenitor cell (EPC) migration and to explore the possible mechanisms. EPCs were treated with metformin, and the migration of EPCs was evaluated by wound healing and Matrigel invasion assays. We also examined the expression levels of of MMP-2 and MMP-9 in EPCs with or without metformin treatment via RT-PCR and western blot analysis, and activities of MMP-2 and MMP-9 in EPCs under different conditions was examined by zymography...
March 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28336389/metformin-ameliorates-uterine-defects-in-a-rat-model-of-polycystic-ovary-syndrome
#14
Yuehui Zhang, Min Hu, Fanci Meng, Xiaoyan Sun, Hongfei Xu, Jiao Zhang, Peng Cui, Njomeza Morina, Xin Li, Wei Li, Xiao-Ke Wu, Mats Brännström, Ruijin Shao, Håkan Billig
Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus...
March 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28333970/-epicatechin-3-o-%C3%AE-d-allopyranoside-from-davallia-formosana-prevents-diabetes-and-dyslipidemia-in-streptozotocin-induced-diabetic-mice
#15
Cheng-Hsiu Lin, Jin-Bin Wu, Jia-Ying Jian, Chun-Ching Shih
The objective of this study was to evaluate the effects and molecular mechanism of (-)-epicatechin-3-O-β-D-allopyranoside from Davallia formosana (BB) (also known as Gu-Sui-Bu) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. This plant was demonstrated to display antioxidant activities and possess polyphenol contents. Diabetic mice were randomly divided into six groups and were given daily oral gavage doses of either BB (at three dosage levels), metformin (Metf) (at 0...
2017: PloS One
https://www.readbyqxmd.com/read/28322845/metformin-like-antidiabetic-cardio-protective-and-non-glycemic-effects-of-naringenin-molecular-and-pharmacological-insights
#16
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
#17
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/28274614/metformin-represses-glucose-starvation-induced-autophagic-response-in-microvascular-endothelial-cells-and-promotes-cell-death
#18
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
#19
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/28265821/suppression-of-rho-kinase-1-is-responsible-for-insulin-regulation-of-the-ampk-srebp-1c-pathway-in-skeletal-muscle-cells-exposed-to-palmitate
#20
Sunyinyan Tang, Wenjun Wu, Wenjuan Tang, Zhijuan Ge, Hongdong Wang, Ting Hong, Dalong Zhu, Yan Bi
AIMS: Clinical and experimental data suggest that early insulin therapy could reduce lipotoxicity in subjects and animal models with type 2 diabetes mellitus. However, the underlying mechanisms need to be clarified. Sterol regulatory element-binding protein 1c (SREBP-1c), which is negatively regulated by AMP-activated protein kinase (AMPK), plays a critical role in lipotoxicity and insulin resistance in skeletal muscle cells. Here, we investigated the effect and molecular mechanism of insulin intervention on the AMPK/SREBP-1c pathway in skeletal muscle cells with chronic exposure to palmitic acid (PA)...
March 7, 2017: Acta Diabetologica
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