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Metformin AND AMPK

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28260041/metformin-suppresses-the-expression-of-sonic-hedgehog-in-gastric-cancer-cells
#7
Zhou Song, Bo Wei, Canrong Lu, Xiaohui Huang, Peiyu Li, Lin Chen
The traditional anti-diabetic drug, metformin, has been found to have anticancer effects. The Sonic hedgehog (Shh) signaling pathway is involved in the on cogenesis of gastric cancer. The aim of the present study was to investigate whether metformin has an effect on the Shh signaling pathway in gastric cancer cells. HGC‑27 and MKN‑45 human gastric cancer cells were treated with metformin at different concentrations and for different durations. Subsequently the mRNA and protein levels of Shh, Smoothened (SMO), and Glioma‑associated oncogene (Gli)‑1, Gli‑2 and Gli‑3 were examined using western blot and reverse transcription‑quantitative polymerase chain reaction analyses...
February 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28258677/metformin-its-potential-anti-cancer-and-anti-aging-effects
#8
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
#9
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/28242651/metformin-suppresses-systemic-autoimmunity-in-roquin-san-san-mice-through-inhibiting-b-cell-differentiation-into-plasma-cells-via-regulation-of-ampk-mtor-stat3
#10
Seon-Yeong Lee, Su-Jin Moon, Eun-Kyung Kim, Hyeon-Beom Seo, Eun-Ji Yang, Hye-Jin Son, Jae-Kyung Kim, Jun-Ki Min, Sung-Hwan Park, Mi-La Cho
Circulating autoantibodies and immune complex deposition are pathological hallmarks of systemic lupus erythematosus (SLE). B cell differentiation into plasma cells (PCs) and some T cell subsets that function as B cell helpers can be therapeutic targets of SLE. Mechanistic target of rapamycin (mTOR) signaling is implicated in the formation of B cells and germinal centers (GCs). We assessed the effect of metformin, which inhibits mTOR, on the development of autoimmunity using Roquin(san/san) mice. Oral administration of metformin inhibited the formation of splenic follicles and inflammation in kidney and liver tissues...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28241849/metformin-potentiates-the-effect-of-arsenic-trioxide-suppressing-intrahepatic-cholangiocarcinoma-roles-of-p38-mapk-erk3-and-mtorc1
#11
Sunbin Ling, Haiyang Xie, Fan Yang, Qiaonan Shan, Haojiang Dai, Jianyong Zhuo, Xuyong Wei, Penghong Song, Lin Zhou, Xiao Xu, Shusen Zheng
BACKGROUND: Arsenic trioxide (ATO) is commonly used in the treatment of acute promyelocytic leukemia (APL), but does not benefit patients with solid tumors. When combined with other agents or radiation, ATO showed treatment benefits with manageable toxicity. Previously, we reported that metformin amplified the inhibitory effect of ATO on intrahepatic cholangiocarcinoma (ICC) cells more significantly than other agents. Here, we investigated the chemotherapeutic sensitization effect of metformin in ATO-based treatment in ICC in vitro and in vivo and explored the underlying mechanisms...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28238946/involvement-of-pregnane-x-receptor-in-the-suppression-of-carboxylesterases-by-metformin-in-vivo-and-in-vitro-mediated-by-the-activation-of-ampk-and-jnk-signaling-pathway
#12
Enfang Shan, Zhu Zhu, Shuangcheng He, Dongbao Chu, Dinghao Ge, Yunran Zhan, Wei Liu, Jian Yang, Jing Xiong
Type 2 diabetes mellitus (T2D) is a complex metabolic disorder requiring polypharmacy treatment in clinic, with metformin being widely used antihyperglycemic drug. However, the mechanisms of metformin as a perpetrator inducing potential drug-drug interactions and adverse drug reactions are scarcely known to date. Carboxylesterases (CESs) are major hydrolytic enzymes highly expressed in the liver, including mouse carboxylesterase 1d (Ces1d) and Ces1e. In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro...
February 24, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28235712/ampk-activation-reduces-the-number-of-atheromata-macrophages-in-apoe-deficient-mice
#13
Jing Wang, Ang Ma, Ming Zhao, Haibo Zhu
BACKGROUND AND AIMS: CC chemokine receptor 2 (Ccr2) governs migration of inflammatory Ly6C(hi) monocytes from the bone marrow (BM) to the circulating blood, which is a key step for macrophage accumulation during progression of atherosclerosis. Hyperlipidemia is often accompanied by low AMP-activated kinase (AMPK) activity and increased expression of Ccr2. The aim of this study was to examine whether there is a link between AMPK and chemokine networks. METHODS: ApoE(-/-) mice were fed a western diet and treated daily with AMPK activators (AICAR, A769662, or Metformin) or vehicle for 10 weeks...
March 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#14
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230250/metformin-attenuates-angiotensin-ii-induced-tgf%C3%AE-1-expression-by-targeting-hepatocyte-nuclear-factor-4%C3%AE
#15
Ruifei Chen, Yenan Feng, Jimin Wu, Yao Song, Hao Li, Qiang Shen, Dan Li, Jianshu Zhang, Zhizhen Lu, Han Xiao, Youyi Zhang
BACKGROUND AND PURPOSE: Metformin, a small molecule antihyperglycaemic agent, is well-known as an AMP-activated protein kinase (AMPK) activator and protects against cardiac fibrosis. However, the underlying mechanisms remain elusive. Transforming growth factor-β1 (TGFβ1) is a key cytokine mediating cardiac fibrosis. Here, we investigated the effects of metformin on TGFβ1 production induced by angiotensin II (AngII) and the underlying mechanisms. EXPERIMENTAL APPROACH: Wild-type and AMPKα2(-/-) C57BL/6 mice were subcutaneously injected with metformin or saline and infused with AngII (3 mg kg(-1) day(-1) ) for 7 days...
February 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28212524/role-of-nrf2-and-protective-effects-of-metformin-against-tobacco-smoke-induced-cerebrovascular-toxicity
#16
Shikha Prasad, Ravi K Sajja, Mohammad Abul Kaisar, Jee Hyun Park, Heidi Villalba, Taylor Liles, Thomas Abbruscato, Luca Cucullo
Cigarette smoking (CS) is associated with vascular endothelial dysfunction in a causative way primarily related to the TS content of reactive oxygen species (ROS), nicotine, and inflammation. TS promotes glucose intolerance and increases the risk of developing type-2 diabetes mellitus (2DM) with which it shares other pathogenic traits including the high risk of cerebrovascular and neurological disorders like stroke via ROS generation, inflammation, and blood-brain barrier (BBB) impairment. Herein we provide evidence of the role played by nuclear factor erythroid 2-related factor (Nrf2) in CS-induced cerebrobvascular/BBB impairments and how these cerebrovascular harmful effects can be circumvented by the use of metformin (MF; a widely prescribed, firstline anti-diabetic drug) treatment...
February 12, 2017: Redox Biology
https://www.readbyqxmd.com/read/28211632/amp-activated-protein-kinase-activator-a-769662-increases-intracellular-calcium-and-atp-release-from-astrocytes-in-an-ampk-independent-manner
#17
Julia M Vlachaki Walker, Josephine L Robb, Ana M Cruz, Amrinder Malhi, Paul G Weightman Potter, Michael L J Ashford, Rory J McCrimmon, Kate L J Ellacott, Craig Beall
AIM: Astrocytes are the main sources of extracellular ATP (eATP) within the brain, which functions as a gliotransmitter, capable of modulating neuronal and astrocytic activity. These cells play an important role in regulating energy homeostasis partly via astrocyte-derived ATP. Given the role of AMPK in regulating intracellular ATP levels, we hypothesised that AMPK may alter ATP release from astrocytes. METHODS: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs)...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#18
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28196954/metformin-and-thyroid-disease
#19
Xianghui Meng, Shuhang Xu, Guofang Chen, Michael Derwahl, Chao Liu
An intriguing area of research in thyroidology is the recently discovered association of insulin resistance with thyroid functional and morphological abnormalities. Individuals with hyperinsulinemia have larger thyroid gland and a higher prevalence of thyroid nodules and cancer. Accordingly, patients treated with metformin have a smaller thyroid volume and a lower risk of incident goiter, thyroid nodule and cancer. Multiple studies in vitro and in vivo have demonstrated that metformin can inhibit the growth of thyroid cells and different types of thyroid cancer cells by affecting the insulin/IGF-1 and mTOR pathways...
February 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28186975/amp-activated-protein-kinase-reduces-inflammatory-responses-and-cellular-senescence-in-pulmonary-emphysema
#20
Xiao-Yu Cheng, Yang-Yang Li, Cheng Huang, Jun Li, Hong-Wei Yao
Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM)...
February 6, 2017: Oncotarget
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