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AMPK AND metformin

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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
#1
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/29344225/metformin-enhances-the-chemosensitivity-of-hepatocarcinoma-cells-to-cisplatin-through-ampk-pathway
#2
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/29343628/keeping-the-home-fires-burning-amp-activated-protein-kinase
#3
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
#4
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/29340030/increased-efficacy-of-metformin-corresponds-to-differential-metabolic-effects-in-the-ovarian-tumors-from-obese-versus-lean-mice
#5
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
https://www.readbyqxmd.com/read/29334602/high-dose-metformin-plus-temozolomide-shows-increased-anti-tumor-effects-in-glioblastoma-in-vitro-and-in-vivo-compared-with-monotherapy
#6
Jung Eun Lee, Ji Hee Lim, Yong Kil Hong, Seung Ho Yang
Purpose: The purpose of the study is to investigate the efficacy of combined treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro and in vivo. Materials and Methods: We investigated the efficacy of combined treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM orthotopic mice model was established by inoculation of 5x105 U87 cells and treated with metformin, TMZ, and the combination for 4 weeks. Western blotting and immunofluorescence of tumor specimens were analyzed to investigate AMP-activated protein kinase (AMPK) and AKT pathway...
January 10, 2018: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/29333122/metformin-enhanced-in-vitro-radiosensitivity-associates-with-g2-m-cell-cycle-arrest-and-elevated-adenosine-5-monophosphate-activated-protein-kinase-levels-in-glioblastoma
#7
Sebastian Adeberg, Denise Bernhardt, Semi B Harrabi, Nils H Nicolay, Juliane Hörner-Rieber, Laila König, Michael Repka, Angela Mohr, Amir Abdollahi, Klaus-Josef Weber, Juergen Debus, Stefan Rieken
Background: It is hypothesized that metabolism plays a strong role in cancer cell regulation. We have recently demonstrated improved progression-free survival in patients with glioblastoma who received metformin as an antidiabetic substance during chemoradiation. Although metformin is well-established in clinical use the influence of metformin in glioblastoma is far from being understood especially in combination with other treatment modalities such as radiation and temozolomide. Materials and Methods: In this study, we examined the influence of metformin in combinations with radiation and temozolomide on cell survival (clonogenic survival), cell cycle (routine flow cytometric analysis, FACScan), and phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho-AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29329611/early-intervention-with-didang-decoction-delays-macrovascular-lesions-in-diabetic-rats-through-regulating-amp-activated-protein-kinase-signaling-pathway
#8
Dan-Dan Ren, Jing Li, Bai Chang, Chun-Shen Li, Ju-Hong Yang
The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups...
November 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#9
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29312569/metformin-improves-nonalcoholic-fatty-liver-disease-in-obese-mice-via-down-regulation-of-apolipoprotein-a5-as-part-of-the-ampk-lxr%C3%AE-signaling-pathway
#10
Min-Jie Lin, Wen Dai, Melanie J Scott, Rong Li, Yi-Qi Zhang, Yang Yang, Lu-Zhu Chen, Xian-Sheng Huang
Apolipoprotein A5 (apoA5) has been implicated in the formation of hepatocyte lipid droplets, a histological hallmark of non-alcoholic fatty liver disease (NAFLD). Recent evidence demonstrated that liver X receptor α (LXRα), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects. In this study we investigated the role of apoA5 and AMPK/LXRα signaling pathway in metformin-related improvement of NAFLD...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306537/metformin-enhances-the-differentiation-of-dental-pulp-cells-into-odontoblasts-by-activating-ampk-signaling
#11
Wei Qin, Xianling Gao, Tao Ma, Michael D Weir, Jing Zou, Bing Song, Zhengmei Lin, Abraham Schneider, Hockin H K Xu
INTRODUCTION: Metformin is a first-line drug for treating type 2 diabetes that regulates the differentiation of mesenchymal stem cells. Its effects on human dental pulp cells (DPCs) remain unknown. This study aimed to investigate the effects of metformin on the proliferation and differentiation of DPCs. METHODS: A live/dead viability assay kit was used to examine the effects of metformin on the cell viability of DPCs. Cell proliferation was analyzed using a cell counting kit (CCK-8; Dojindo, Tokyo, Japan)...
January 3, 2018: Journal of Endodontics
https://www.readbyqxmd.com/read/29286156/metformin-induced-activation-of-ampk-inhibits-the-proliferation-and-migration-of-human-aortic-smooth-muscle-cells-through-upregulation-of-p53-and-ifi16
#12
Biao Hao, Yan Xiao, Fang Song, Xiangshu Long, Jing Huang, Maobo Tian, Shiyan Deng, Qiang Wu
The proliferation and migration of vascular smooth muscle cells are significant in the development and progression of atherosclerosis and plaque rupture. Metformin is a widely used antidiabetic drug, which has been reported to inhibit cell growth and migration. The antiproliferative and antimigratory effects of metformin have been attributed to 5' adenosine monophosphate-activated protein kinase (AMPK) activation. The purpose of the present study was to investigate the effects of metformin on primary human aortic muscle cells (HASMCs) in vitro and to clarify the underlying mechanism...
December 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285837/the-new-metformin-derivative-hl156a-prevents-oral-cancer-progression-by-inhibiting-the-igf-akt-mtor-pathways
#13
Thuy Giang Lam, Yun Soo Jeong, Soo-A Kim, Sang-Gun Ahn
Metformin is a biguanide widely prescribed as an antidiabetic drug for type 2 diabetes mellitus patients. The purpose of this study was to observe the effects of the new metformin derivative, HL156A, on human oral cancer cell and to investigate its possible mechanisms. It was observed that HL156A significantly decreased FaDu and YD-10B cell viability and colony formation in a dose dependent manner. HL156A also markedly reduced wound closure and migration of FaDu and YD-10B cells. We observed that HL156A decreased mitochondrial membrane potential and induced ROS levels and apoptotic cells with caspase-3 and -9 activation...
December 29, 2017: Cancer Science
https://www.readbyqxmd.com/read/29285650/synergistic-cytotoxicity-of-the-dipeptidyl-peptidase-iv-inhibitor-gemigliptin-with-metformin-in-thyroid-carcinoma-cells
#14
Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Seong Jin Lee
PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor, gemigliptin alone or in combination with metformin on survival, proliferation, and migration of thyroid carcinoma cells was investigated. METHODS: SW1736 and TPC-1 human thyroid carcinoma cells were used. RESULTS: Gemigliptin and metformin caused cell death in a dose-dependent manner. In cells treated with both gemigliptin and metformin, compared with metformin alone, all of the combination index values were lower than 1...
December 28, 2017: Endocrine
https://www.readbyqxmd.com/read/29278707/metformin-ameliorates-activation-of-hepatic-stellate-cells-and-hepatic-fibrosis-by-succinate-and-gpr91-inhibition
#15
Giang Nguyen, So Young Park, Cong Thuc Le, Won Sun Park, Dae Hee Choi, Eun-Hee Cho
BACKGROUND: Chronic liver disease is becoming a major cause of morbidity and mortality worldwide. During liver injury, hepatic stellate cells (HSCs) trans-differentiate into activated myofibroblasts, which produce extracellular matrix. Succinate and succinate receptor (G-protein coupled receptor91, GPR91) signaling pathway has now emerged as a regulator of metabolic signaling. A previous study showed that succinate and its specific receptor, GPR91, are involved in the activation of HSCs and the overexpression of α-smooth muscle actin (α-SMA)...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29250169/therapeutic-strategies-against-cancer-stem-cells-in-human-colorectal-cancer
#16
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Piotr Spychalski, Zbigniew Kmieć
Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29246951/metformin-mediates-protection-against-legionella-pneumonia-through-activation-of-ampk-and-mitochondrial-reactive-oxygen-species
#17
Chiaki Kajiwara, Yu Kusaka, Soichiro Kimura, Tetsuo Yamaguchi, Yuta Nanjo, Yoshikazu Ishii, Heiichiro Udono, Theodore J Standiford, Kazuhiro Tateda
In Legionella pneumophila infection, macrophages play a critical role in the host defense response. Metformin, an oral drug for type 2 diabetes, is attracting attention as a new supportive therapy against a variety of diseases, such as cancer and infectious diseases. The novel mechanisms for metformin actions include modulation of the effector functions of macrophages and other host immune cells. In this study, we have examined the effects of metformin on L. pneumophila infection in vitro and in vivo. Metformin treatment suppressed growth of L...
December 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29245964/phenformin-has-anti-tumorigenic-effects-in-human-ovarian-cancer-cells-and-in-an-orthotopic-mouse-model-of-serous-ovarian-cancer
#18
Amanda L Jackson, Wenchuan Sun, Joshua Kilgore, Hui Guo, Ziwei Fang, Yajie Yin, Hannah M Jones, Timothy P Gilliam, Chunxiao Zhou, Victoria L Bae-Jump
Obesity and diabetes have been associated with increased risk and worse outcomes in ovarian cancer (OC). The biguanide metformin is used in the treatment of type 2 diabetes and is also believed to have anti-tumorigenic benefits. Metformin is highly hydrophilic and requires organic cation transporters (OCTs) for entry into human cells. Phenformin, another biguanide, was taken off the market due to an increased risk of lactic acidosis over metformin. However, phenformin is not reliant on transporters for cell entry; and thus, may have increased potency as both an anti-diabetic and anti-tumorigenic agent than metformin...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227654/synergistic-chemopreventive-and-therapeutic-effects-of-co-drug-ua-met-implication-in-tumor-metastasis
#19
Guirong Zheng, Zhichun Shen, Aixiao Xu, Kai Jiang, Pengyu Wu, Xiang Yang, Xian Chen, Jingwei Shao
The anticancer properties of ursolic acid (UA) and metformin (Met) have been well demonstrated. However, whether these compounds can act synergistically to prevent and treat cancer is not known. We present in this study, the synergism between UA and Met, and that of a new codrug made of UA and Met (UA-Met) against several cancer cell lines. The combination of high concentration of UA (25, 50, 75, 100 μM) and Met (5, 10, 20, 40 mM) resulted in synergetic cytotoxicity on MDA-MB-231 and MCF-7 cells (CI < 0...
December 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29196297/acetylsalicylic-acid-governs-the-effect-of-sorafenib-in-ras-mutant-cancers
#20
Heinz Hammerlindl, Dinoop Ravindran Menon, Sabrina Hammerlindl, Abdullah Al Emran, Joachim Torrano, Katrin Sproesser, Divya Thakkar, Min Xiao, Victoria G Atkinson, Brian Gabrielli, Nikolas K Haass, Meenhard Herlyn, Clemens Krepler, Helmut Schaider
PURPOSE: Identify and characterize novel combinations of sorafenib with anti-inflammatory painkillers to target difficult to treat RAS-mutant cancer. EXPERIMENTAL DESIGN: The cytotoxicity of acetylsalicylic acid (aspirin) in combination with the multikinase inhibitor sorafenib (Nexavar) was assessed in RAS-mutant cell lines in vitro. The underlying mechanism for the increased cytotoxicity was investigated using selective inhibitors and shRNA-mediated gene knockdown...
December 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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