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https://www.readbyqxmd.com/read/29777629/mechanisms-of-metformin-action-in-and-out-of-the-gut
#1
EDITORIAL
Takahiro Minamii, Munenobu Nogami, Wataru Ogawa
One hundred years have passed since guanidine, a precursor compound of biguanides and thus of metformin, was found to have a glucose-lowering effect in live animals1 . In this historical study, C. K. Watanabe1 did not set out to identify glucose-lowering agents but rather to understand the mechanism underlying the development of tetany in animals that have undergone parathyroidectomy. Watanabe 1 concluded that guanidine is a pathogenic factor responsible for tetany because its administration in rabbits resulted in "tetany-like" muscle cramps associated with low blood glucose levels...
May 19, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29774060/metformin-prevents-nerve-growth-factor-dependent-proliferative-and-proangiogenic-effects-in-epithelial-ovarian-cancer-cells-and-endothelial-cells
#2
Maritza P Garrido, Carolina Vera, Margarita Vega, Andrew F G Quest, Carmen Romero
Background: Epithelial ovarian cancer (EOC) is characterized by exacerbated angiogenesis regulated by proangiogenic and growth factors. Nerve growth factor (NGF) is overexpressed in EOC where it promotes proliferation as well as survival and is considered a proangiogenic factor. Metformin, a drug commonly used in the treatment of diabetes, is attributed to antineoplastic effects, but the underlying mechanisms remain unknown. Given that current therapies yield modest results in EOC patients, the aim of this study was to determine the effects of metformin on NGF-enhanced proliferation of EOC cells and the angiogenic potential of endothelial cells...
2018: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29773082/no-detectable-differential-microrna-expression-between-non-atherosclerotic-arteries-of-type-2-diabetic-patients-treated-or-untreated-with-metformin-and-non-diabetic-patients
#3
Lasse Bach Steffensen, Søren Feddersen, Simone Rørdam Preil, Lars Melholt Rasmussen
BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor of cardiovascular disease (CVD), however, the underlying mechanisms are largely unknown. Using non-atherosclerotic internal thoracic arteries (ITAs) obtained from coronary artery bypass grafting, we previously identified a distinct elevation in the level of proteins comprising the arterial basement membrane in T2DM patients not treated with metformin. Altered transcription of genes encoding these proteins has not been observed, indicating alternative mechanisms of dysregulation...
May 17, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29762537/the-cardioprotective-effect-of-metformin-in-doxorubicin-induced-cardiotoxicity-the-role-of-autophagy
#4
Rita Zilinyi, Attila Czompa, Andras Czegledi, Andrea Gajtko, Dora Pituk, Istvan Lekli, Arpad Tosaki
The molecular mechanisms underlying doxorubicin-induced cardiotoxicity are still being investigated, but are known to involve oxidative stress, mitochondrial dysfunction, and the dysregulation of autophagy. The objective of the current study was to examine the protective role of metformin and its effect on autophagy in doxorubicin-induced cardiotoxicity. Sprague⁻Dawley rats were divided into four groups at random. The doxorubicin-treated group received doxorubicin (3 mg/kg every second day) intraperitoneally...
May 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29753686/pharmacological-inhibition-of-the-mitochondrial-nadph-oxidase-4-pkc%C3%AE-gal-3-pathway-reduces-left-ventricular-fibrosis-following-myocardial-infarction
#5
Maria Del Carmen Asensio-Lopez, Antonio Lax Perez, Maria Josefa Fernandez Del Palacio, Yassine Sassi, Roger J Hajjar, Domingo A Pascual-Figal
Although the initial reparative fibrosis after myocardial infarction (MI) is crucial for preventing rupture of the ventricular wall, an exaggerated fibrotic response and reactive fibrosis outside the injured area are detrimental. Although metformin prevents adverse cardiac remodeling, as well as provides glycemic control, the underlying mechanisms remain poorly documented. This study describes the effect of mitochondrial NADPH oxidase 4 (mitoNox) and protein kinase C-alpha (PKCα) on the cardiac fibrosis and galectin 3 (Gal-3) expression...
April 23, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29746885/curcumin-inhibits-hepatic-stellate-cell-activation-via-suppression-of-succinate-associated-hif-1%C3%AE-induction
#6
Linlin She, Dan Xu, Zixia Wang, Yirui Zhang, Qingli Wei, Jiye Aa, Guangji Wang, Baolin Liu, Yuan Xie
PURPOSE: Aberrant succinate accumulation emerges as a unifying mechanism for inflammation and oxidative stress. This study aims to investigate whether curcumin ameliorates hepatic fibrosis via blocking succinate signaling. METHODS: We investigated the effects of curcumin on hepatic succinate accumulation and liver fibrosis in mice fed a high-fat diet (HFD). Meanwhile, we stimulated mouse primary hepatic stellate cells (HSCs) with succinate and observed the inhibitory effects of curcumin on succinate signaling...
May 7, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29738369/cardioprotective-effects-of-metformin
#7
Christine Driver, Kayode Dominion Samuel Bamitale, Aniessa Kazi, Mehnaaz Olla, Annah Ntsoaki Nyane, Peter Mark Oroma Owira
Metformin, routinely used as first-line drug in the treatment of type 2 diabetes has been shown to have cardioprotective effects beyond its glycemic control. These have been attributed to increases in Akt concentrations and activation of protein kinases in the RISK pathways. which prevent the mitochondrial mPTP from opening and rupturing it and therefore protects myocyte viability. In myocardial infarction and subsequent reperfusion, metformin activation of AMPK promotes glycolysis and keeps the mPTP closed...
May 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29737290/pharmacoeconomic-evaluation-of-glimepiride-combined-with-other-drugs-in-the-treatment-of-diabetes
#8
Xiufang Liu, Liping Zeng, Wenchao Xu
The goal of diabetic drug treatment is to stabilize the blood sugar for a long time to close to the normal level, to correct the metabolic disorder and eliminate the symptoms. At present, glimepiride has become commonly used drugs for the treatment of diabetes with obesity. Compared with metformin, acarbose and rosiglitazone, glimepiride has different mechanisms of drug action, clinical combination showed synergistic hypoglycemic effect, good clinical curative effect. So, we use three treatments to study as group A (glimepiride and metformin); group B (glimepiride and acarbose); Group C (glimepiride and rosiglitazone)...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29735458/pharmacoeconomic-evaluation-of-glimepiride-combined-with-other-drugs-in-the-treatment-of-diabetes
#9
Xiufang Liu, Liping Zeng, Wenchao Xu
The goal of diabetic drug treatment is to stabilize the blood sugar for a long time to close to the normal level, to correct the metabolic disorder and eliminate the symptoms. At present, glimepiride has become commonly used drugs for the treatment of diabetes with obesity. Compared with metformin, acarbose and rosiglitazone, glimepiride has different mechanisms of drug action, clinical combination showed synergistic hypoglycemic effect, good clinical curative effect. So, we use three treatments to study as group A (glimepiride and metformin); group B (glimepiride and acarbose); Group C (glimepiride and rosiglitazone)...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29729383/ameliorative-potential-of-lavandula-stoechas-in-metabolic-syndrome-via-multitarget-interactions
#10
S S Kulabas, H Ipek, A R Tufekci, S Arslan, I Demirtas, R Ekren, U Sezerman, T B Tumer
ETHNOPHARMACOLOGICAL IMPORTANCE: Decoction and infusion prepared from aerial parts of Lavandula stoechas L. (L. stoechas) have been traditionally used as remedy against several components of metabolic syndrome (MetS) and associated disorders including type II diabetes and cardiovascular diseases by Anatolian people. AIM OF THE STUDY: The aim is to elucidate the potential ameliorative effects of L. stoechas aqueous extracts on insulin resistance and inflammation models through multitarget in vitro approaches and also to elucidate mechanism of action by analyzing transcriptional and metabolic responses...
May 2, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29728363/increased-hepatic-pdgf-aa-signaling-mediates-liver-insulin-resistance-in-obesity-associated-type-2-diabetes
#11
Amar Abderrahmani, Loïc Yengo, Robert Caiazzo, Mickaël Canouil, Stéphane Cauchi, Violeta Raverdy, Valérie Plaisance, Valérie Pawlowski, Stéphane Lobbens, Julie Maillet, Laure Rolland, Raphael Boutry, Gurvan Queniat, Maxime Kwapich, Mathie Tenenbaum, Julien Bricambert, Sophie Saussenthaler, Elodie Anthony, Pooja Jha, Julien Derop, Olivier Sand, Iandry Rabearivelo, Audrey Leloire, Marie Pigeyre, Martine Daujat-Chavanieu, Sabine Gerbal-Chaloin, Tasnim Dayeh, Guillaume Lassailly, Philippe Mathurin, Bart Staels, Johan Auwerx, Annette Schürmann, Catherine Postic, Clemens Schafmayer, Jochen Hampe, Amélie Bonnefond, François Pattou, Philippe Froguel
In type 2 diabetes (T2D), hepatic insulin resistance is strongly associated with non-alcoholic fatty liver disease (NAFLD). In this study, we hypothesized that DNA methylome of livers from patients with T2D, when compared to livers of individuals with normal plasma glucose levels, can unveil some mechanism of hepatic insulin resistance that could link to NAFLD. Using DNA methylome and transcriptome analyses of livers from obese individuals, we found that both hypomethylation at a CpG site in PDGFA (encoding platelet derived growth factor alpha) and PDGFA overexpression are associated with increased T2D risk, hyperinsulinemia, increased insulin resistance and increased steatohepatitis risk...
May 4, 2018: Diabetes
https://www.readbyqxmd.com/read/29726618/metformin-s-antitumour-and-anti-angiogenic-activities-are-mediated-by-skewing-macrophage-polarization
#12
Ji-Chang Wang, Xin Sun, Qiang Ma, Gui-Feng Fu, Long-Long Cong, Hong Zhang, De-Fu Fan, Jun Feng, Shao-Ying Lu, Jian-Lin Liu, Guang-Yue Li, Pei-Jun Liu
Beneficial effects of metformin on cancer risk and mortality have been proved by epidemiological and clinical studies, thus attracting research interest in elucidating the underlying mechanisms. Recently, tumour-associated macrophages (TAMs) appeared to be implicated in metformin-induced antitumour activities. However, how metformin inhibits TAMs-induced tumour progression remains ill-defined. Here, we report that metformin-induced antitumour and anti-angiogenic activities were not or only partially contributed by its direct inhibition of functions of tumour and endothelial cells...
May 4, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29725482/metformin-inhibits-the-proliferation-and-metastasis-of-osteosarcoma-cells-by-suppressing-the-phosphorylation-of-akt
#13
Zuohong Li, Lesheng Wang, Nan Luo, Yantao Zhao, Jiazhi Li, Qiwei Chen, Yu Tian
Metformin (Met) is a therapeutic agent for the treatment of type 2 diabetes mellitus. There is evidence that Met may reduce the risk of cancer in patients with type 2 diabetes mellitus by inhibiting tumor cell growth, prolonging the overall survival time in patients with various types of malignancy. However, the function and mechanism of Met have not been fully elucidated in osteosarcoma (OS). The present study evaluated the anti-proliferative effect of Met on MG63 and U2OS OS cells, identifying that it acted in a dose- and time-dependent manner...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29713286/the-wnt-signaling-pathway-effector-tcf7l2-mediates-olanzapine-induced-weight-gain-and-insulin-resistance
#14
Ranran Li, Jianjun Ou, Li Li, Ye Yang, Jingping Zhao, Renrong Wu
Olanzapine is a widely used atypical antipsychotic medication for treatment of schizophrenia and is often associated with serious metabolic abnormalities including weight gain and impaired glucose tolerance. These metabolic side effects are severe clinical problems but the underpinning mechanism remains poorly understood. Recently, growing evidence suggests that Wnt signaling pathway has a critical role in the pathogenesis of schizophrenia and molecular cascades of antipsychotics action, of which Wnt signaling pathway key effector TCF7L2 is strongly associated with glucose homeostasis...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29710715/targeting-insulin-for-alzheimer-s-disease-mechanisms-status-and-potential-directions
#15
Jung Hyun Lee, Jordan B Jahrling, Larry Denner, Kelly T Dineley
Insulin resistance can occur when the body is unable to respond to insulin even in excess. In the brain, insulin manages glucose metabolism in regions such as the hippocampus and plays a key role in directly regulating ERK, a kinase required for the type of memory compromised in early Alzheimer's disease (AD). Human imaging studies show that brain glucose utilization declines with age and is notably impaired in subjects with early AD. Likewise, animal models of AD or insulin resistance, or both, demonstrate that dysfunctional insulin signaling and insulin resistance in the brain have reciprocity with neuroinflammation and aberrant accumulation of amyloid-β (Aβ), pathological hallmarks in AD...
April 27, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29704494/metformin-a-first-line-drug-for-type-2-diabetes-mellitus-disrupts-the-malat1-mir-142-3p-sponge-to-decrease-invasion-and-migration-in-cervical-cancer-cells
#16
Chenglai Xia, Shaofeng Liang, Zhihong He, Xiaolan Zhu, Ruihong Chen, Jinman Chen
The molecular mechanisms underlying the anti-neoplastic properties of metformin, a first-line drug for type 2 diabetes, remain elusive. To explore the novel anti-neoplastic mechanisms of metformin, the transwell chamber and wound-healing assays were used to evaluate its effects on the migration and invasion of human cervical cancer cells. Real-time PCR and Western blotting were used to measure the gene and protein expression, respectively, of microRNA (miRNA) miR-142-3p, long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript-1 (MALAT1), and high-mobility group AT-hook 2 (HMGA2)...
April 25, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29702167/pumpkin-polysaccharide-modifies-the-gut-microbiota-during-alleviation-of-type-2-diabetes-in-rats
#17
Guimei Liu, Li Liang, Guoyong Yu, Quanhong Li
Pumpkin polysaccharide is able to alleviate diabetes, but understanding of the underlining mechanism is still limited. In this study, we hypothesized that the alleviating effects of pumpkin polysaccharide is modulated via changes in the gut microbiota and short-chain fatty acid (SCFA) production in type 2 diabetic rats. After the type 2 diabetic model successfully was established, three groups of high-fat diet induced diabetic rats were intragastrically administered pumpkin polysaccharide, metformin, or saline solution respectively...
April 24, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29698747/neuroprotective-effects-of-metformin-on-traumatic-brain-injury-in-rats-associated-with-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathway
#18
Li Tao, Di Li, Huixiang Liu, Feng Jiang, Yitian Xu, Gang Chen, Ying Cao, Rong Gao
Traumatic brain injury (TBI) triggers a complex sequence of inflammatory responses that contribute to secondary injury. Metformin, a first-line drug used to treat type 2 diabetes, is reported to exhibit potent anti-inflammatory activity on diseases associated with the central nervous system (CNS). The aim of this study is to investigate the potential neuroprotective effects of metformin on acute brain injury after TBI and explore the underlying mechanisms. Male Sprague-Dawley (SD) rats were divided into four groups: sham group, TBI group, TBI + saline (NS) group and TBI + metformin group...
April 23, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29687194/roll-compaction-and-tableting-of-high-loaded-metformin-formulations-using-efficient-binders
#19
Oscar-Rupert Arndt, Peter Kleinebudde
Metformin has a poor tabletability and flowability. Therefore, metformin is typically wet granulated with a binder before tableting. To save production costs, it would be desirable to implement a roll compaction/dry granulation (RCDG) process for metformin instead of using wet granulation. In order to implement RCDG, the efficiency of dry binders is crucial to ensure a high drug load and suitable properties of dry granules and tablets. This study evaluates dry granules manufactured by RCDG and subsequently tableting of high metformin content formulations (≥ 87...
April 23, 2018: AAPS PharmSciTech
https://www.readbyqxmd.com/read/29684379/effect-of-a-long-term-treatment-with-metformin-in-dystrophic-mdx-mice-a-reconsideration-of-its-potential-clinical-interest-in-duchenne-muscular-dystrophy
#20
Paola Mantuano, Francesca Sanarica, Elena Conte, Maria Grazia Morgese, Roberta Francesca Capogrosso, Anna Cozzoli, Adriano Fonzino, Angelo Quaranta, Jean-Francois Rolland, Michela De Bellis, Giulia Maria Camerino, Luigia Trabace, Annamaria De Luca
The pharmacological stimulation of AMP-activated protein kinase (AMPK) via metabolic enhancers has been proposed as potential therapeutic strategy for Duchenne muscular dystrophy (DMD). Metformin, a widely-prescribed anti-hyperglycemic drug which activates AMPK via mitochondrial respiratory chain, has been recently tested in DMD patients in synergy with nitric oxide (NO)-precursors, with encouraging results. However, preclinical data supporting the use of metformin in DMD are still poor, and its actions on skeletal muscle appear controversial...
April 20, 2018: Biochemical Pharmacology
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