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Metformin AND AMPK

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https://www.readbyqxmd.com/read/28817623/metformin-attenuates-myocardial-ischemia-reperfusion-injury-via-up-regulation-of-antioxidant-enzymes
#1
Xiaoling Wang, Lei Yang, Licheng Kang, Jing Li, Liang Yang, Jincai Zhang, Jie Liu, Mengmeng Zhu, Qiong Zhang, Yanna Shen, Zhi Qi
The objective was to examine the protective effect of metformin (Met) on myocardial ischemia-reperfusion (IR) injury and whether the mechanism was related to the AMPK/ antioxidant enzymes signaling pathway. Rat Langendorff test and H2O2-treated rat cardiomyocytes (H9c2) were used in this study. Met treatment significantly improved left ventricular (LV) function, reduced infarct size and CK-MB release in comparison with IR group. Decreased TUNEL staining positive cells were also observed in IR+Met group ex vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28816632/the-liver-circadian-clock-modulates-biochemical-and-physiological-responses-to-metformin
#2
Emma Henriksson, Anne-Laure Huber, Erin K Soto, Anna Kriebs, Megan E Vaughan, Drew Duglan, Alanna B Chan, Stephanie J Papp, Madelena Nguyen, Megan E Afetian, Katja A Lamia
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice...
August 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28801594/deficiency-in-catechol-o-methyltransferase-is-linked-to-a-disruption-of-glucose-homeostasis-in-mice
#3
Megumi Kanasaki, Swayam Prakash Srivastava, Fan Yang, Ling Xu, Sumiyo Kudoh, Munehiro Kitada, Norikazu Ueki, Hyoh Kim, Jinpeng Li, Satoru Takeda, Keizo Kanasaki, Daisuke Koya
2-methoxyestradiol (2-ME), an estrogen metabolite generated via catechol-o-methyltransferase (COMT), is multifunctional methoxy-catechol. Here, we report that COMT deficiency leads to glucose intolerance and 2-ME rescues COMT-deficient-associated metabolic defects. Liver COMT protein was suppressed in high fat diet (HFD)-fed or in pregnant mice. COMT suppression, by Ro41-0960 or siRNA, in HFD fed mice or in pregnant mice exacerbated glucose intolerance; 2-ME intervention ameliorated these defects. 2-ME effects on glucose tolerance were associated with AMPK phosphorylation in the liver and in islet cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28791738/metformin-promotes-neuronal-differentiation-and-neurite-outgrowth-through-ampk-activation-in-human-bone-marrow-mesenchymal-stem-cells
#4
Min-Ji Ahn, Goang-Won Cho
Metformin is an AMP-activated kinase (AMPK) activator that plays a role in glucose energy metabolism and cell protection. It is widely used to treat several diseases, including type 2 diabetes, cardiovascular diseases, cancer, and metabolic diseases. In this study, we investigated whether AMPK activation upon treatment with metformin may promote neurite outgrowth during the progression of neuronal differentiation in human bone marrow-mesenchymal stem cells (hBM-MSCs). Differentiation of metformin-treated MSCs (Met-MSCs to Met-diMSCs) in the neuronal induction media resulted in an increase in the number of differentiated cells in a metformin concentration-dependent manner...
August 9, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28791487/metformin-attenuates-the-tlr4-inflammatory-pathway-in-skeletal-muscle-of-diabetic-rats
#5
Leonardo Gomes Peixoto, Renata Roland Teixeira, Danielle Diniz Vilela, Lara Naves Barbosa, Douglas Carvalho Caixeta, Simone Ramos Deconte, Fernanda de Assis de Araújo, Robinson Sabino-Silva, Foued Salmen Espindola
AIMS: Inflammation induced by hyperglycemia triggers the toll-like receptor (TLR) pathway into cells. Our hypothesis was that metformin treatment attenuates the TLR signaling pathways triggered by inflammation in skeletal muscle of hypoinsulinemic/hyperglycemic STZ-induced rats. Thus, we examined TLR signaling under hypoinsulinemia and hyperglycemia conditions and its correlation with insulin resistance in muscle of diabetic rats treated with metformin. METHODS: Ten-day diabetic rats were submitted to 7 days of saline (D group) or metformin (500 mg/kg once per day) (D + M group)...
August 9, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28791376/macc1-induces-autophagy-to-regulate-proliferation-apoptosis-migration-and-invasion-of-squamous-cell-carcinoma
#6
Jian Wu, Dawei Zhang, Jun Li, Xin Deng, Guannan Liang, Yang Long, Xuemei He, Tianyang Dai, Delian Ren
Metastasis-associated colon cancer-1 (MACC1) plays an important role in cancer development, but the role and mechansim of MACC1 in squamous cell carcinoma (ESCC) remain unclear. In this study, we found that MACC1 expression was increased in ESCC, and correlated with lymph node metastasis. MACC1 knockdown suppresed ESCC cell proliferation, metastasis and enchanced cell apoptosis. Moreover, MACC1 knockdown inhibited ESCC cell autophagy, and 3-methyladenine was able to rescue MACC1-induced malignant phenotype of ESCC cells...
August 8, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28776086/the-mechanisms-of-action-of-metformin
#7
REVIEW
Graham Rena, D Grahame Hardie, Ewan R Pearson
Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration...
August 3, 2017: Diabetologia
https://www.readbyqxmd.com/read/28769124/metformin-inhibits-cyst-formation-in-a-zebrafish-model-of-polycystin-2-deficiency
#8
Ming-Yang Chang, Tsu-Lin Ma, Cheng-Chieh Hung, Ya-Chung Tian, Yung-Chang Chen, Chih-Wei Yang, Yi-Chuan Cheng
Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse models of PKD1. However, metformin has not been studied in animal models of PKD2, and the cellular mechanism underlying its effectiveness is not entirely clear. This study investigated the effects of metformin on cyst formation in a zebrafish model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post fertilisation and observed pronephric cyst formation by using the wt1b promoter-driven GFP signal in Tg(wt1b:GFP) pkd2 morphants...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28767685/histone-deacetylase-inhibition-prevents-cell-death-induced-by-loss-of-tricellular-tight-junction-proteins-in-temperature-sensitive-mouse-cochlear-cells
#9
Kenichi Takano, Takuya Kakuki, Yakuto Kaneko, Takayuki Kohno, Shin Kikuchi, Tetsuo Himi, Takashi Kojima
Tricellular tight junctions (tTJs) are specialized structures that occur where the corners of three cells meet to seal adjacent intercellular space. The molecular components of tTJs include tricellulin (TRIC) and lipolysis-stimulated lipoprotein receptor (LSR) which recruits TRIC, are required for normal hearing. Although loss of TRIC causes hearing loss with degeneration of cochlear cells, the detailed mechanisms remains unclear. In the present study, by using temperature-sensitive mouse cochlear cells, US/VOT-E36 cell line, we investigated the changes of TRIC and LSR during cochlear cell differentiation and the effects of histone deacetylase (HDAC) inhibitors against cell degeneration induced by loss of TRIC and LSR...
2017: PloS One
https://www.readbyqxmd.com/read/28766983/lkb1-ampk-modulates-nutrient-induced-changes-in-the-mode-of-division-of-intestinal-epithelial-crypt-cells-in-mice
#10
Katherine Blackmore, Weinan Zhou, Megan J Dailey
Nutrient availability influences intestinal epithelial stem cell proliferation and tissue growth. Increases in food result in a greater number of epithelial cells, villi height and crypt depth. We investigated whether this nutrient-driven expansion of the tissue is the result of a change in the mode of intestinal epithelial stem cell division and if LKB1-AMPK signaling plays a role. We utilized in vivo and in vitro experiments to test this hypothesis. C57BL/6J mice were separated into four groups and fed varying amounts of chow for 18 h: (1) ad libitum, (2) 50% of their average daily intake (3) fasted or (4) fasted for 12 h and refed...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28755883/metformin-insights-into-its-anticancer-potential-with-special-reference-to-ampk-dependent-and-independent-pathways
#11
REVIEW
Shoeb Ikhlas, Masood Ahmad
Metformin has been known for its antidiabetic effects for decades and is used as a first line therapy in type 2 diabetes. But recently its anticancer potential has also been discovered. Metformin targets many pathways that play an important role in cancer cell proliferation and angiogenesis, mTORC1 signaling is a crucial pathway among them. Metformin inhibits mTORC1 via AMPK dependent and AMPK independent pathways, thereby inhibiting cancer cell growth and development. Encouraged by positive results of numerous preclinical studies on various types of cancer, many clinical trials are underway to study metformin's effect in chemoprevention and treatment of cancers in humans...
July 26, 2017: Life Sciences
https://www.readbyqxmd.com/read/28752417/metformin-alleviated-the-neuronal-oxidative-stress-in-hippocampus-of-rats-under-single-prolonged-stress
#12
Jiangang Wang, Bing Xiao, Fang Han, Yuxiu Shi
In an animal model of post-traumatic stress disorder (PTSD), our previous studies showed mitochondrial stress-induced apoptosis in the hippocampus. Metformin, the most commonly prescribed anti-diabetic drug, exerts its effects through 5'-adenosine monophosphate-activated protein kinase (AMPK) activation. It was shown that a neuroprotective role was gradually established against stroke, spinal cord injury and Parkinson's disease. The aim of this study was to explore the role of the AMPK pathway in neuronal apoptosis in the hippocampus using a rat model of PTSD...
July 27, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28751004/polyphenols-activate-energy-sensing-network-in-insulin-resistant-models
#13
Radika Mutlur Krishnamoorthy, Anuradha Carani Venkatraman
Unhealthy diet deficient in fruits and vegetables but rich in calories is considered to be one factor responsible for the increased prevalence of insulin resistance and type 2 diabetes (T2D). The consumption of fast foods and soft drinks increases fructose consumption per se and this is of major concern since prolonged fructose intake induces insulin resistance and thereby T2D. The energy homeostasis is regulated by a network consisting of "fuel gauze" called AMP-activated protein kinase (AMPK), the NAD(+) dependent type III deacetylase (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) which is disrupted in T2D...
July 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28744157/the-abc7-regimen-a-new-approach-to-metastatic-breast-cancer-using-seven-common-drugs-to-inhibit-epithelial-to-mesenchymal-transition-and-augment-capecitabine-efficacy
#14
Richard E Kast, Nicolas Skuli, Samuel Cos, Georg Karpel-Massler, Yusuke Shiozawa, Ran Goshen, Marc-Eric Halatsch
Breast cancer metastatic to bone has a poor prognosis despite recent advances in our understanding of the biology of both bone and breast cancer. This article presents a new approach, the ABC7 regimen (Adjuvant for Breast Cancer treatment using seven repurposed drugs), to metastatic breast cancer. ABC7 aims to defeat aspects of epithelial-to-mesenchymal transition (EMT) that lead to dissemination of breast cancer to bone. As add-on to current standard treatment with capecitabine, ABC7 uses ancillary attributes of seven already-marketed noncancer treatment drugs to stop both the natural EMT process inherent to breast cancer and the added EMT occurring as a response to current treatment modalities...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28732480/metformin-and-longevity-metal-a-window-of-opportunity-study-investigating-the-biological-effects-of-metformin-in-localised-prostate-cancer
#15
Danielle Crawley, Ashish Chandra, Massimo Loda, Cheryl Gillett, Paul Cathcart, Ben Challacombe, Gary Cook, Declan Cahill, Aida Santa Olalla, Fidelma Cahill, Gincy George, Sarah Rudman, Mieke Van Hemelrijck
BACKGROUND: Metformin is a biguanide oral hypoglycaemic agent commonly used for the treatment of type 2 diabetes mellitus. In addition to its anti-diabetic effect, metformin has also been associated with a reduced risk of cancer incidence of a number of solid tumours, including prostate cancer (PCa). However, the underlying biological mechanisms for these observations have not been fully characterised in PCa. One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic action as elevated insulin and insulin like growth factor - 1 (IGF-1) levels play a role in PCa development and progression...
July 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28729062/pharmacological-activation-of-ampk-inhibits-incision-evoked-mechanical-hypersensitivity-and-the-development-of-hyperalgesic-priming-in-mice
#16
Michael D Burton, Dipti V Tillu, Khadijah Mazhar, Galo L Mejia, Marina N Asiedu, Kufreobong Inyang, Travis Hughes, Bo Lian, Gregory Dussor, Theodore J Price
New therapeutics to manage post-surgical pain are needed to mitigate the liabilities of opioid and other analgesics. Our previous work shows that key modulators of excitability in peripheral nociceptors, such as extracellular signal-regulated kinases (ERK) are inhibited by activation of adenosine monophosphate activated protein kinase (AMPK). We hypothesized that AMPK activation would attenuate acute incision-evoked mechanical hypersensitivity and the development of hyperalgesic priming caused by surgery in mice...
July 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28720775/metformin-ameliorates-the-phenotype-transition-of-peritoneal-mesothelial-cells-and-peritoneal-fibrosis-via-a-modulation-of-oxidative-stress
#17
Hyun-Soo Shin, Jiyeon Ko, Dal-Ah Kim, Eun-Sun Ryu, Hye-Myung Ryu, Sun-Hee Park, Yong-Lim Kim, Eok-Soo Oh, Duk-Hee Kang
Phenotype transition of peritoneum is an early mechanism of peritoneal fibrosis. Metformin, 5'-adenosine monophosphate-activated protein kinase (AMPK) activator, has recently received a new attention due to its preventive effect on organ fibrosis and cancer metastasis by inhibiting epithelial-to-mesenchymal transition (EMT). We investigated the effect of metformin on EMT of human peritoneal mesothelial cells (HPMC) and animal model of peritoneal dialysis (PD). TGF-β1-induced EMT in HPMC was ameliorated by metformin...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714409/ampk-therapeutic-target-for-diabetes-and-cancer-prevention
#18
Shotaro Umezawa, Takuma Higurashi, Atsushi Nakajima
BACKGROUND: AMP-activated protein kinase (AMPK) is a protein kinase that maintains homeostasis in cells and organs. As a master regulator of metabolism, AMPK coordinates many metabolic reactions. AMPK is a key factor in diabetes and metabolic syndrome associated with dysregulation of the metabolic status. Recently, AMPK has also attracted attention as a tumor suppressor. The aim of this article is to discuss about the role of AMPK in diabetes as well as cancer and to evaluate its effectiveness in treatment and prevention of these diseases...
July 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28709719/metformin-effects-on-the-heart-and-the-cardiovascular-system-a%C3%A2-review-of-experimental-and-clinical-data
#19
REVIEW
L Nesti, A Natali
BACKGROUND: Metformin, the eldest and most widely used glucose lowering drug, is likely to be effective also on cardiac and vascular disease prevention. Nonetheless, uncertainty still exists with regard to its effects on the cardiovascular system as a whole and specifically on the myocardium, both at the organ and cellular levels. METHODS: We reviewed the available data on the cardiac and vascular effects of metformin, encompassing both in vitro, either tissue or isolated organ, and in vivo studies in experimental animals and humans, as well as the evidence generated by major clinical trials...
May 10, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28699677/metformin-ameliorates-bscb-disruption-by-inhibiting-neutrophil-infiltration-and-mmp-9-expression-but-not-direct-tj-proteins-expression-regulation
#20
Di Zhang, Qian Tang, Gang Zheng, Chenggui Wang, Yifei Zhou, Yaosen Wu, Jun Xuan, Naifeng Tian, Xiangyang Wang, Yan Wu, Huazi Xu, Xiaolei Zhang
Blood-spinal cord barrier (BSCB) disruption is a major process for the secondary injury of spinal cord injury (SCI) and is considered to be a therapeutic target for SCI. Previously, we demonstrated that metformin could improve functional recovery after SCI; however, the effect of metformin on BSCB is still unknown. In this study, we found that metformin could prevent the loss of tight junction (TJ) proteins at day 3 after SCI in vivo, but in vitro there was no significant difference of these proteins between control and metformin treatment in endothelial cells...
July 12, 2017: Journal of Cellular and Molecular Medicine
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