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https://www.readbyqxmd.com/read/28643448/post-conditioning-with-metformin-attenuates-apoptotic-events-in-cardiomyoblasts-associated-with-ischemic-reperfusion-injury
#1
Rajesh Ramachandran, Mini S
Ischemic post-conditioning is considered as a potent method to combat ischemic reperfusion injury than pre-conditioning since the latter is non predictive and risky. Rapid initiation of reperfusion with potent anti oxidant compound can be one of the most effective treatments to reduce the infract size and behavioural deficits as a result of ischemic insult. Apoptosis/Necrotic events undisputedly hold significant role in determining the fate of cardiomyocytes post ischemic injury but current studies are speculative regrading the role of post-conditioning in maintaining cellular homeostasis...
June 23, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28642704/quercetin-a-lead-compound-against-type-2-diabetes-ameliorates-glucose-uptake-via-ampk-pathway-in-skeletal-muscle-cell-line
#2
R Dhanya, A D Arya, P Nisha, P Jayamurthy
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28635413/the-high-responder-a-review-of-pathophysiology-and-outcomes-during-ivf-treatment
#3
Mariano Mascarenhas, Adam H Balen
This review attempts to summarize the known literature on high responders to ovarian stimulation during assisted reproductive techniques (ART). Response to gonadotrophins is subject to significant interindividual and intercycle variation, thus carrying a risk of high response or poor response to ovarian stimulation regimens. The main risk for high responders is the development of ovarian hyperstimulation syndrome (OHSS) which is associated with significant morbidity. Hence, the definition of high responders in the literature has primarily focussed on risk factors for OHSS...
February 28, 2017: Human Fertility: Journal of the British Fertility Society
https://www.readbyqxmd.com/read/28634570/to-use-or-not-to-use-metformin-in-cerebral-ischemia-a-review-of-the-application-of-metformin-in-stroke-rodents
#4
REVIEW
Isaac Arbeláez-Quintero, Mauricio Palacios
Ischemic strokes are major causes of death and disability. Searching for potential therapeutic strategies to prevent and treat stroke is necessary, given the increase in overall life expectancy. Epidemiological reports indicate that metformin is an oral antidiabetic medication that can reduce the incidence of ischemic events in patients with diabetes mellitus. Its mechanism of action has not been elucidated, but metformin pleiotropic effects involve actions in addition to glycemic control. AMPK activation has been described as one of the pharmacological mechanisms that explain the action of metformin and that lead to neuroprotective effects...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28628912/liver-kinase-b1-amp-activated-protein-kinase-pathway-activation-attenuated-the-progression-of-endotoxemia-in-the-diabetic-mice
#5
Yan Yang, Ruolan Dong, Danli Hu, Zhihui Chen, Menglu Fu, Dao Wen Wang, Xizhen Xu, Ling Tu
BACKGROUND/AIMS: Sepsis is a common disease that continues to increase in prevalence worldwide, and diabetes mellitus may make the situation worse. This study was designed to determine the role of Liver Kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in diabetic mice complicated with systemic endotoxemia. METHODS: The effects of LKB1/AMPK signaling pathway activation on endotoxemia were investigated in streptozotocin induced diabetic mice (STZ-mice) and db/db diabetic mice...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28621714/acute-effect-of-metformin-on-postprandial-hypertriglyceridemia-through-delayed-gastric-emptying
#6
Daisuke Sato, Katsutaro Morino, Fumiyuki Nakagawa, Koichiro Murata, Osamu Sekine, Fumiaki Beppu, Naohiro Gotoh, Satoshi Ugi, Hiroshi Maegawa
Postprandial hypertriglyceridemia is a potential target for cardiovascular disease prevention in patients with diabetic dyslipidemia. Metformin has been reported to reduce plasma triglyceride concentrations in the postprandial states. However, little is known about the mechanisms underlying the triglyceride-lowering effect of metformin. Here, we examined the effects of metformin on lipid metabolism after olive oil-loading in 129S mice fed a high fat diet for three weeks. Metformin administration (250 mg/kg) for one week decreased postprandial plasma triglycerides...
June 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28619690/metformin-the-aspirin-of-the-21-st-century-its-role-in-gestational-diabetes-prevention-of-preeclampsia-and-cancer-and-the-promotion-of-longevity
#7
REVIEW
Roberto Romero, Offer Erez, Maik Hüttemann, Eli Maymon, Bogdan Panaitescu, Agustin Conde-Agudelo, Percy Pacora, Bo Hyun Yoon, Lawrence I Grossman
Metformin is everywhere. Originally introduced in clinical practice as an anti-diabetic agent, its role as a therapeutic agent is expanding to include treatment of pre-diabetes, gestational diabetes, polycystic ovarian disease, and more recently, experimental studies, as well as observations in randomized clinical trials, suggest that metformin could have a place in the treatment or prevention of preeclampsia. This article provides a brief overview of the history of metformin in the treatment of diabetes, reviews the results of meta-analyses of metformin in gestational diabetes, and the treatment of obese non-diabetic pregnant women to prevent macrosomia...
June 12, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28618992/modulating-mitophagy-in-mitochondrial-disease
#8
Eszter Dombi, Heather Mortiboys, Joanna Poulton
Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28618017/curcumin-and-metformin-mediated-chemoprevention-of-oral-cancer-is-associated-with-inhibition-of-cancer-stem-cells
#9
Gangotri Siddappa, Safeena Kulsum, Doddathimmasandra Ramanjanappa Ravindra, Vinay V Kumar, Nalini Raju, Nisheena Raghavan, Holalugunda Vittalamurthy Sudheendra, Anupam Sharma, Sumsum P Sunny, Tina Jacob, Binu T Kuruvilla, Merina Benny, Benny Antony, Mukund Seshadri, Padma Lakshminarayan, Wesley Hicks, Amritha Suresh, Moni A Kuriakose
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin, are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4NQO (4-nitro-quinoline-oxide) induced, mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven, oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40 to 100 fold) and protein levels (p≤0...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28611284/activation-of-the-atf2-creb-pgc-1%C3%AE-pathway-by-metformin-leads-to-dopaminergic-neuroprotection
#10
Hojin Kang, Rin Khang, Sangwoo Ham, Ga Ram Jeong, Hyojung Kim, Minkyung Jo, Byoung Dae Lee, Yun Il Lee, Areum Jo, Chi Hu Park, Hyein Kim, Jeongkon Seo, Sun Ha Paek, Yun-Song Lee, Jeong-Yun Choi, Yunjong Lee, Joo-Ho Shin
Progressive dopaminergic neurodegeneration is responsible for the canonical motor deficits in Parkinson's disease (PD). The widely prescribed anti-diabetic medicine metformin is effective in preventing neurodegeneration in animal models; however, despite the significant potential of metformin for treating PD, the therapeutic effects and molecular mechanisms underlying dopaminergic neuroprotection by metformin are largely unknown.In this study, we found that metformin induced substantial proteomic changes, especially in metabolic and mitochondrial pathways in the substantia nigra (SN)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611100/ampk-activation-enhances-the-anti-atherogenic-effects-of-high-density-lipoproteins-in-apoe-mice
#11
Ang Ma, Jing Wang, Liu Yang, Yuanyuan An, Haibo Zhu
HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE-/-) mice fed with a high fat diet. After administration, although there no changes in serum lipid levels among the groups...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28606032/metformin-a-new-era-for-an-old-drug-in-the-treatment-of-immune-mediated-disease
#12
Mark Schuiveling, Nadia Vazirpanah, Timothy R D J Radstake, Maili Zimmermann, Jasper C A Broen
Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its potential anti-inflammatory properties. Metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production. Among key immune events, this results in inhibited monocyte to macrophage differentiation and restrained inflammatory capacity of activated macrophages...
June 12, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28600118/so-many-antihyperglycemics-how-to-choose-a-practical-approach
#13
Alice Y Y Cheng
Guidelines from around the world have stressed the importance of glycemic control in the management of patients with type 2 diabetes (T2DM) to reduce the risk of developing complications. To achieve this goal, both lifestyle and pharmacologic therapies are available. There are 9 classes of antihyperglycemic therapies available in Canada and each class provides a different mechanism of action to address the pathophysiology of T2DM. Metformin remains the first choice for pharmacologic therapy. Thereafter, individualization is essential...
June 6, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28590925/suppression-of-hypoxia-induced-excessive-angiogenesis-by-metformin-via-elevating-tumor-blood-perfusion
#14
Ji-Chang Wang, Guang-Yue Li, Ping-Ping Li, Xin Sun, Wei-Ming Li, Yan Li, Shao-Ying Lu, Pei-Jun Liu
The anti-diabetic metformin has been demonstrated to be effective in suppression of tumor progression via multiple mechanisms, in which angiogenic inhibition is involved. Hypoxia is a common feather of malignant tumor and promotes angiogenesis via induction of pro-angiogenic factors. However, the effect of metformin on tumor hypoxia and the association with angiogenic inhibition are still unclear. In the current study, we investigated the effects of metformin on both tumor blood perfusion and hypoxia-induced excessive angiogenesis...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#15
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28586073/effects-of-the-tangningtongluo-formula-as-an-alternative-strategy-for-diabetics-via-upregulation-of-insulin-receptor-substrate-1
#16
Long Cheng, Junmei Song, Geng Li, Yue Liu, Yuming Wang, Xiangbao Meng, Guibo Sun, Xiaobo Sun
Tangningtongluo (TNTL), a traditional Chinese medicine, has been widely used in clinics for decades in southwest China. Its pharmacological properties and underlying molecular mechanisms remain unclear. The main goal of ethnopharmacology is to identify novel bioactive compounds derived from plants for use in indigenous medical practice. This knowledge can be used to develop novel pharmaceuticals. In the present study, hyperglycemic C57BL/KsJ‑db/db (db/db) mice were used to test the effect of TNTL on microvasculature of the retina and hypoglycemia...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28580278/fgf21-does-not-require-adipocyte-amp-activated-protein-kinase-ampk-or-the-phosphorylation-of-acetyl-coa-carboxylase-acc-to-mediate-improvements-in-whole-body-glucose-homeostasis
#17
Emilio P Mottillo, Eric M Desjardins, Andreas M Fritzen, Vito Z Zou, Justin D Crane, Julian M Yabut, Bente Kiens, Derek M Erion, Adhiraj Lanba, James G Granneman, Saswata Talukdar, Gregory R Steinberg
OBJECTIVE: Fibroblast growth factor 21 (FGF21) shows great potential for the treatment of obesity and type 2 diabetes, as its long-acting analogue reduces body weight and improves lipid profiles of participants in clinical studies; however, the intracellular mechanisms mediating these effects are poorly understood. AMP-activated protein kinase (AMPK) is an important energy sensor of the cell and a molecular target for anti-diabetic medications. This work examined the role of AMPK in mediating the glucose and lipid-lowering effects of FGF21...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28579909/the-alleviative-effects-of-metformin-for-lipopolysaccharide-induced-acute-lung-injury-rat-model-and-its-underlying-mechanism
#18
Xiangcheng Zhang, Futai Shang, Liangliang Hui, Kui Zang, Gengyun Sun
For patients who have sepsis, acute lung injury (ALI) causes most of death. Metformin (Met) is an anti-hyperglycemic agent and it has extensive pharmacological properties. This study aimed to analyze the influence of Met on lipopolysaccharide (LPS) -induced ALI. Met (1, 2, and 4 mg/kg) were injected and LPS was injected 30 min later. The data suggested Met can reduce release of inflammatory cytokines and bronchoalveolar lavage fluid (BALF) protein expression, reduce lung wet/dry ratio, and significantly improve LPS-induced lung destruction during ALI...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28579457/metformin-ameliorates-gender-and-age-dependent-hemodynamic-instability-and-myocardial-injury-in-murine-hemorrhagic-shock
#19
Dzmitry Matsiukevich, Giovanna Piraino, Patrick Lahni, Paul W Hake, Vivian Wolfe, Michael O'Connor, Jeanne James, Basilia Zingarelli
Severity of multiple organ failure is significantly impacted by age and gender in patients with hemorrhagic shock. However, the molecular mechanisms underlying the enhanced organ injury are not fully understood. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of metabolic responses during stress. We investigated whether hemorrhage-induced myocardial injury is age and gender dependent and whether treatment with metformin, an AMPK activator, affords cardioprotective effects. C57/BL6 young (3-5months) and mature (9-12months) male and female mice were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with blood and Lactated Ringer's solution...
June 1, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28576465/metformin-and-caffeic-acid-regulate-metabolic-reprogramming-in-human-cervical-carcinoma-siha-htb-35%C3%A2-cells-and-augment-anticancer-activity-of-cisplatin-via-cell-cycle-regulation
#20
Malgorzata Tyszka-Czochara, Karolina Bukowska-Strakova, Marcin Majka
Metformin shows benefits in anticancer prevention in humans. In this study, normal human fibroblasts (FB) and metastatic cervical cancer cells (SiHa) were exposed to 10 mM Metformin (Met), 100 μM Caffeic Acid (trans-3,4-dihydroxycinnamic acid, CA) or combination of the compounds. Both drugs were selectively toxic towards cancer cells, but neither Met nor CA treatment suppressed growth of normal cells. Met and CA regulated metabolic reprogramming in SiHa tumor cells through different mechanisms: Met suppressed regulatory enzymes Glurtaminase (GLS) and Malic Enzyme 1 (ME1) and enhanced pyruvate oxidation via tricarboxylic acids (TCA) cycle, while CA acted as glycolytic inhibitor...
May 30, 2017: Food and Chemical Toxicology
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