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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/28730750/improving-type-2-diabetes-mellitus-glycaemic-outcomes-is-possible-without-spending-more-on-medication-lessons-from-the-uk-national-diabetes-audit
#2
Adrian H Heald, Mark Livingston, Nagaraj Malipatil, Michal Becher, Joyce Craig, Mike Stedman, Anthony A Fryer
OBJECTIVES: There is continuing discussion globally about how to optimise outcomes for type 2 diabetes (T2DM) patients. In the UK, national (NICE) guidance was updated in 2016 (NG28). We aimed to determine the factors at a GP practice level that relate to glycaemic control outcome. METHODS: Data was accessed from 4,050 GP practices (GPP) (50% of total) covering 1.6 million T2DM patients in the UK National Diabetes Audit 2013-14 and 2014-15. This reported T2DM population characteristics, services and outcomes, including % total glycaemic control (TGC) (at 67...
July 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28717335/evaluation-of-therapeutic-effectiveness-of-prescribed-medications-in-patients-with-type-2-diabetes-mellitus-findings-from-a-tertiary-care-hospital-lahore-pakistan
#3
Bareera Rana, Allah Bukhsh, Tahir Mehmood Khan, Ammar Sarwar, Muhammad Ovais Omer, Shazia Qasim Jamshed
AIM: The present study was aimed to highlight the current prescribing pattern of oral hypoglycemia in type 2 diabetes mellitus and to evaluate the therapeutic effectiveness of these therapeutic categories in achieving target glycemic control. METHODS: This is a prospective, cross-sectional, observational study of 6 months' duration conducted in a tertiary care hospital of Lahore, Pakistan. RESULTS: The current research recruited 145 patients presented in diabetes management center of a tertiary care hospital in Lahore, Pakistan...
April 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28714409/ampk-therapeutic-target-for-diabetes-and-cancer-prevention
#4
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/28712591/normalizing-ovulation-rate-by-preferential-reduction-of-hepato-visceral-fat-in-adolescent-girls-with-polycystic-ovary-syndrome
#5
Lourdes Ibáñez, Luis Del Río, Marta Díaz, Giorgia Sebastiani, Óscar J Pozo, Abel López-Bermejo, Francis de Zegher
PURPOSE: Polycystic ovary syndrome (PCOS) is an increasingly prevalent disorder in adolescent girls, commonly presenting with hirsutism/oligomenorrhea, commonly treated with an oral contraceptive (OC), and commonly followed by oligoanovulatory subfertility. We tested whether an intervention targeting the reduction of hepato-visceral adiposity is followed by a higher ovulation rate than OC treatment. METHODS: This randomized, open-label, single-center, pilot proof-of-concept study (12 months on treatment, then 12 months off) was performed in adolescent girls with hirsutism and oligomenorrhea (PCOS by National Institutes of Health; no sexual activity; N = 36; mean age 16 years, body mass index 23...
July 13, 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#6
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/28703902/prevalence-and-characteristics-of-paediatric-type-2-diabetes-in-the-republic-of-ireland
#7
M I O'Dea, S M O'Connell, M J O'Grady
OBJECTIVE: To establish the prevalence of paediatric Type 2 diabetes in the Republic of Ireland and describe patient demographics, initial presentation, management, outcomes, comorbidities and complications. METHODS: Using a standardized proforma we conducted a cross-sectional survey of children and adolescents aged < 16 years with a diagnosis of Type 2 diabetes between October and December 2015 in each of the 19 centres in the Republic of Ireland responsible for the care of children with diabetes...
July 13, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
https://www.readbyqxmd.com/read/28700249/simulation-based-evaluation-of-dose-titration-algorithms-for-rapid-acting-insulin-in-subjects-with-type-2-diabetes-mellitus-inadequately-controlled-on-basal-insulin-and-oral-antihyperglycemic-medications
#8
Xiaosu Ma, Jenny Y Chien, Jennal Johnson, James Malone, Vikram Sinha
BACKGROUND: The purpose of this prospective, model-based simulation approach was to evaluate the impact of various rapid-acting mealtime insulin dose-titration algorithms on glycemic control (hemoglobin A1c [HbA1c]). METHODS: Seven stepwise, glucose-driven insulin dose-titration algorithms were evaluated with a model-based simulation approach by using insulin lispro. Pre-meal blood glucose readings were used to adjust insulin lispro doses. Two control dosing algorithms were included for comparison: no insulin lispro (basal insulin+metformin only) or insulin lispro with fixed doses without titration...
July 12, 2017: Diabetes Technology & Therapeutics
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
#9
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
#10
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/28698627/the-energy-disruptor-metformin-targets-mitochondrial-integrity-via-modification-of-calcium-flux-in-cancer-cells
#11
Camille Loubiere, Stephan Clavel, Jerome Gilleron, Rania Harisseh, Jeremy Fauconnier, Issam Ben-Sahra, Lisa Kaminski, Kathiane Laurent, Stephanie Herkenne, Sandra Lacas-Gervais, Damien Ambrosetti, Damien Alcor, Stephane Rocchi, Mireille Cormont, Jean-François Michiels, Bernard Mari, Nathalie M Mazure, Luca Scorrano, Alain Lacampagne, Abdallah Gharib, Jean-François Tanti, Frederic Bost
Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake of calcium into the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the disorganization of the cristae and inner mitochondrial membrane in several cancer cells and tumors. Mechanistically, these alterations were found to be due to calcium entry into the mitochondria, because the swelling induced by metformin was reversed by the inhibition of mitochondrial calcium uniporter (MCU)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692586/bioactivity-and-prostate-tissue-distribution-of-metformin-in-a-preprostatectomy-prostate-cancer-cohort
#12
Mike M Nguyen, Jessica A Martinez, Chiu-Hsieh Hsu, Mitchell Sokoloff, Robert S Krouse, Blake A Gibson, Raymond B Nagle, Howard L Parnes, Catherine Cordova, H-H Sherry Chow
Metformin has recently been shown to have potential to reduce prostate cancer risk. We conducted a randomized, double-blind, placebo-controlled trial to determine the modulating effects of metformin on tissue and systemic biomarkers of drug activity and its distribution into the prostate tissue. Twenty patients with prostate cancer scheduled to undergo prostatectomy were randomly assigned to receive either extended-release metformin or placebo for a median of 34 days before surgery. Prostatectomy and serum samples were analyzed for metformin concentrations, serum biomarkers of drug activity (prostate-specific antigen, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein 3, sex hormone-binding globulin, and testosterone) and tissue biomarkers of proliferation, apoptosis, cell cycle regulation, and mTOR inhibition...
July 7, 2017: European Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28685671/experimental-models-for-aging-and-their-potential-for-novel-drug-discovery
#13
Jaume Folch, Oriol Busquets, Miren EttchetoElena Sánchez-López, Mercè Pallàs, Carlos Beas-Zarate, Miguel Marin, Gemma Casadesus, Jordi Olloquequi, Carme Auladell, Antoni Camins
The development of antiaging drugs is an interesting area of scientific research. In order to evaluate the beneficial effects of new potential drugs, it is necessary to gather the specific knowledge on the adequate preclinical models that are available. This review focuses on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend lifespan and health span. Dietary restriction (DR), a common experimental process to extend lifespan in all organisms, is also discussed...
July 7, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28684424/il-4-upregulates-cyclooxygenase-1-expression-in-macrophages
#14
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/28676020/current-and-potential-future-pharmacological-approaches-for-non-alcoholic-fatty-liver-disease
#15
Konstantinos Imprialos, Konstantinos Stavropoulos, Sofia Bouloukou, Georgios Kerpiniotis, Asterios Karagiannis, Michael Doumas
BACKGOUND: Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the general population. The disease ranges from simple steatosis, to non-alcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. Several drugs are used in daily clinical practice to manage the disease. However, data on their efficacy in liver histology are not consistent. AIM: We discuss current treatment options for NAFLD and NASH and preliminary results from novel drugs under investigation...
June 20, 2017: Current Vascular Pharmacology
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
#16
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
https://www.readbyqxmd.com/read/28666833/ludwigia-octovalvis-extract-improves-glycemic-control-and-memory-performance-in-diabetic-mice
#17
Wei-Sheng Lin, Jung-Hsin Lo, Jo-Hsuan Yang, Hao-Wei Wang, Shou-Zen Fan, Jui-Hung Yen, Pei-Yu Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. AIM OF THE STUDY: We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK)...
June 27, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28651817/angiogenesis-and-cancer-stem-cells-new-perspectives-on-therapy-of-ovarian-cancer
#18
REVIEW
Anna Markowska, Stefan Sajdak, Janina Markowska, Adam Huczyński
Failure in ovarian cancer therapy, following cytoreduction and chemotherapy, is related to the presence of cancer stem cells - a small subpopulation of cells resistant to chemotherapy and irradiation - in the tumour which may cause cancer relapse and manifestation of metastases. Therapies targeted at Cancer Stem Cells (CSCs), such as those employing metformin (a drug used in the treatment of diabetes type II) and salinomycin, an antibiotic isolated from Streptococcus albus bacteria, seem promising. Anti-angiogenic therapy with bevacizumab was found to be effective in all phases of ovarian cancer treatment...
June 20, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28651479/evaluating-the-short-term-cost-effectiveness-of-liraglutide-versus-lixisenatide-in-patients-with-type-2-diabetes-in-the-united-states
#19
B Hunt, C C McConnachie, C Gamble, T Dang-Tan
AIMS: Bringing patients with type 2 diabetes to recommended glycated hemoglobin (HbA1c) treatment targets can reduce the risk of developing diabetes-related complications. The aim of the present analysis was to evaluate the short-term cost-effectiveness of once-daily liraglutide 1.8 mg vs once-daily lixisenatide 20 μg as an add-on to metformin for treatment of type 2 diabetes in the US by assessing the cost per patient achieving HbA1c-focused and composite treatment targets. MATERIALS AND METHODS: Percentages of patients achieving recommended targets were obtained from the LIRA-LIXI trial, which compared the efficacy and safety of once-daily liraglutide 1...
July 11, 2017: Journal of Medical Economics
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
#20
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
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