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https://www.readbyqxmd.com/read/28731034/regulation-of-hepatic-glucose-metabolism-in-health-and-disease
#1
REVIEW
Max C Petersen, Daniel F Vatner, Gerald I Shulman
The liver is crucial for the maintenance of normal glucose homeostasis - it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes...
July 21, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28729113/activation-of-rage-stat3-pathway-by-methylglyoxal-contributes-to-spinal-central-sensitization-and-persistent-pain-induced-by-bortezomib
#2
Jia-You Wei, Cui-Cui Liu, Han-Dong Ouyang, Chao Ma, Man-Xiu Xie, Meng Liu, Wan-Long Lei, Huan-Huan Ding, Shao-Ling Wu, Wen-Jun Xin
Bortezomib is a first-line chemotherapeutic drug widely used for multiple myeloma and other nonsolid malignancies. Although bortezomib-induced persistent pain is easily diagnosed in clinic, the pathogenic mechanism remains unclear. Here, we studied this issue with use of a rat model of systemic intraperitoneal administration of bortezomib for consecutive 5days. Consisted with our previous study, we found that bortezomib treatment markedly induced mechanical allodynia in rats. Furthermore, we first found that bortezomib treatment significantly induced the upregulation of methylglyoxal in spinal dorsal horn of rats...
July 18, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28729062/pharmacological-activation-of-ampk-inhibits-incision-evoked-mechanical-hypersensitivity-and-the-development-of-hyperalgesic-priming-in-mice
#3
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/28725599/effects-of-metformin-on-endothelial-health-and-erectile-dysfunction
#4
REVIEW
Jay Pravin Patel, Eric Hweegeun Lee, Carlos Ignacio Mena, Charles N Walker
Erectile dysfunction (ED) affects approximately 18 million American men. ED may be attributed to several etiologies, including arteriogenic, psychogenic, neurogenic, hormonal, drug-induced, and systemic disease or aging related factors. Specific to arteriogenic ED, three major mechanisms have been identified: (I) endothelium-dependent vasodilatory impairment; (II) sympathetic nerve activity elevation; (III) atherosclerotic luminal narrowing. Additionally, these insults have been linked to the insulin resistant state, which in turn is comorbid with obesity, dyslipidemia, diabetes, and hypertension...
June 2017: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28722177/metformin-induced-alterations-in-nucleotide-metabolism-cause-5-fluorouracil-resistance-but-gemcitabine-susceptibility-in-oesophageal-squamous-cell-carcinoma
#5
Charissa Mynhardt, Leonard Howard Damelin, Rupal Jivan, Jade Peres, Sharon Prince, Robin Bruce Veale, Demetra Mavri-Damelin
5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5-year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti-cancer activity, in combination with 5-FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5-FU in WHCO1 and WHCO5 cells, by more than 5-fold and 6-fold respectively, as assessed by MTT assay...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28720775/metformin-ameliorates-the-phenotype-transition-of-peritoneal-mesothelial-cells-and-peritoneal-fibrosis-via-a-modulation-of-oxidative-stress
#6
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/28719077/metformin-synergistic-pemetrexed-suppresses-non-small-cell-lung-cancer-cell-proliferation-and-invasion-in-vitro
#7
Yan Zhang, Xiuli Feng, Tao Li, Erpan Yi, Yu Li
The aim of this study was to investigate whether metformin in combination with pemetrexed has an effect on the treatment of non-small-cell lung cancer (NSCLC) models and to explore the related molecular mechanism. The half maximal inhibitory concentration (IC50) and combination index (CI) of metformin and pemetrexed were detected by the CCK8 assay to assess the antiproliferative and therapeutic effects of the two-drug combination. Flow cytometry (FCM) and invasion assays were used to estimate the variation in apoptosis rate and invasion ability of the differently treated NSCLC cell lines...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28717133/insulin-upregulates-betatrophin-expression-via-pi3k-akt-pathway
#8
Puhan Lu, Xi Chen, Zeqing Zhang, Jianhua Zhang, Yan Yang, Zhelong Liu, Junhui Xie, Shiying Shao, Xinrong Zhou, Shuhong Hu, Wentao He, Jiajun Zhao, Xuefeng Yu
Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714409/ampk-therapeutic-target-for-diabetes-and-cancer-prevention
#9
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/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#10
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28708400/contribution-of-mate1-to-renal-secretion-of-the-nmda-receptor-antagonist-memantine
#11
Fabian Müller, Dietmar Weitz, Volker Derdau, Martin Sandvoss, Katharina Mertsch, Jörg König, Martin F Fromm
The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was the examination of the interaction of memantine with OCT2 and MATEs. Memantine transporter inhibition and transport were examined in HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers of single- (MDCK-OCT2, MDCK-MATE1) and double-transfected MDCK cells (MDCK-OCT2-MATE1) were used for studies on vectorial, basal to apical memantine transport...
July 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28702329/metformin-causes-a-futile-intestinal-hepatic-cycle-which-increases-energy-expenditure-and-slows-down-development-of-a-type-2-diabetes-like-state
#12
Philipp Schommers, Anna Thurau, Insa Bultmann-Mellin, Maria Guschlbauer, Andreas R Klatt, Jan Rozman, Martin Klingenspor, Martin Hrabe de Angelis, Jens Alber, Dirk Gründemann, Anja Sterner-Kock, Rudolf J Wiesner
OBJECTIVE: Metformin, the first line drug for treatment of type 2 diabetes, suppresses hepatic gluconeogenesis and reduces body weight in patients, the latter by an unknown mechanism. METHODS: Mice on a high fat diet were continuously fed metformin in a therapeutically relevant dose, mimicking a retarded formulation. RESULTS: Feeding metformin in pharmacologically relevant doses to mice on a high fat diet normalized HbA1c levels and ameliorated glucose tolerance, as expected, but also considerably slowed down weight gain...
July 2017: Molecular Metabolism
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
#13
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
https://www.readbyqxmd.com/read/28698800/metformin-induced-ablation-of-microrna-21-5p-releases-sestrin-1-and-cab39l-antitumoral-activities
#14
Claudio Pulito, Federica Mori, Andrea Sacconi, Frauke Goeman, Maria Ferraiuolo, Patrizia Pasanisi, Carlo Campagnoli, Franco Berrino, Maurizio Fanciulli, Rebecca J Ford, Massimo Levrero, Natalia Pediconi, Ludovica Ciuffreda, Michele Milella, Gregory R Steinberg, Mario Cioce, Paola Muti, Sabrina Strano, Giovanni Blandino
Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy. Our analysis here revealed that the expression of miR-21-5p was downregulated in multiple breast cancer cell lines treated with pharmacologically relevant doses of metformin...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28689771/immunosuppression-with-tacrolimus-improved-implantation-and-rescued-expression-of-uterine-progesterone-receptor-and-its-co-regulators-fkbp52-and-piasy-at-nidation-in-the-obese-and-diabetic-mice-comparative-studies-with-metformin
#15
Ahmad J H Albaghdadi, Frederick W K Kan
Diabesity is often associated with subfertility and recurrent miscarriages. Evidence links systemic and local uterine cytotoxicity to the pathogenesis of implantation failure (IF) in diabetes. Immunosuppression with tacrolimus improved pregnancy outcomes in obese and diabetic mice and repeated IF in women with elevated Th1/Th2 blood cell ratios. However the mode of action of tacrolimus in protecting against IF and the molecular mechanisms associated with recurrent miscarriages in the obese and diabetic subjects are yet to be elucidated...
July 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28684424/il-4-upregulates-cyclooxygenase-1-expression-in-macrophages
#16
Ashley E Shay, Bastihalli T Diwakar, Bo-Jhih Guan, Vivek Narayan, Joseph F Urban, K Sandeep Prabhu
Macrophages use various cell-surface receptors to sense their environment and undergo polarized responses. The cytokines IL-4 and IL-13, released from T-helper type 2 (Th2) cells, drive macrophage polarization toward an alternatively activated phenotype (M2). This phenotype is associated with the expression of potent pro-resolving mediators, such as the prostaglandin (PG) D2-derived cyclopentenone metabolite, 15d-PGJ2, produced by the cyclooxygenase (Ptgs; Cox) pathway. Interestingly, IL-4 treatment of bone marrow-derived macrophages significantly downregulates Cox-2 protein expression, while Cox-1 levels are significantly increased...
July 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28681986/metformin-associated-prevention-of-weight-gain-in-insulin-treated-type-2-diabetic-patients-cannot-be-explained-by-decreased-energy-intake-a-post-hoc-analysis-of-a-randomized-placebo-controlled-4-3-year-trial
#17
Mattijs Out, Ida Miedema, Harriët Jager-Wittenaar, Cees van der Schans, Wim Krijnen, Philippe Lehert, Coen Stehouwer, Adriaan Kooy
Metformin prevents weight gain in patients with type 2 diabetes (T2D). However, the mechanisms involved are still unknown. In this post-hoc analysis of the HOME trial, we aimed to determine whether metformin affects energy intake. Patients with T2D were treated with 850 mg metformin or placebo (1-3 times daily) added to insulin for 4.3 years. Dietary intake was assessed at baseline, after 1 year and after 4.3 years, according to the dietary history method. Of the 310 included participants, 179 completed (93 placebo, 86 metformin) all three dietary assessments...
July 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28681917/concentration-dependent-metabolic-effects-of-metformin-in-healthy-and-fanconi-anemia-lymphoblast-cells
#18
Silvia Ravera, Vanessa Cossu, Barbara Tappino, Elena Nicchia, Carlo Dufour, Simona Cavani, Andrea Sciutto, Claudia Bolognesi, Marta Columbaro, Paolo Degan, Enrico Cappelli
Metformin (MET) is the drug of choice for patients with type 2 diabetes and has been proposed for use in cancer therapy and for treating other metabolic diseases. More than 14,000 studies have been published addressing the cellular mechanisms affected by MET. However, several in vitro studies have used concentrations of the drug 10-100-fold higher than the plasmatic concentration measured in patients. Here we evaluated the biochemical, metabolic and morphologic effects of various concentrations of MET. Moreover, we tested the effect of MET on Fanconi Anemia (FA) cells, a DNA repair genetic disease with defects in energetic and glucose metabolism, as well as on human promyelocytic leukemia (HL60) cell lines...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28677234/anti-aging-pharmacology-in-cutaneous-wound-healing-effects-of-metformin-resveratrol-and-rapamycin-by-local-application
#19
Pan Zhao, Bing-Dong Sui, Nu Liu, Ya-Jie Lv, Chen-Xi Zheng, Yong-Bo Lu, Wen-Tao Huang, Cui-Hong Zhou, Ji Chen, Dan-Lin Pang, Dong-Dong Fei, Kun Xuan, Cheng-Hu Hu, Yan Jin
Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects...
July 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28673572/elimination-of-cancer-stem-cells-and-reactivation-of-latent-hiv-1-via-ampk-activation-common-mechanism-of-action-linking-inhibition-of-tumorigenesis-and-the-potential-eradication-of-hiv-1
#20
Jahahreeh Finley
Although promising treatments are currently in development to slow disease progression and increase patient survival, cancer remains the second leading cause of death in the United States. Cancer treatment modalities commonly include chemoradiation and therapies that target components of aberrantly activated signaling pathways. However, treatment resistance is a common occurrence and recent evidence indicates that the existence of cancer stem cells (CSCs) may underlie the limited efficacy and inability of current treatments to effectuate a cure...
July 2017: Medical Hypotheses
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