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AMPK AND glitazone

İlhan Elmaci, Meric A Altinoz
Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L)...
October 2016: Biochemical Genetics
Michela Cetrone, Antonietta Mele, Domenico Tricarico
The skeletal muscle atrophy and sarcopenia are negative prognostic factors in the treatment of the diabetic aged-population. Insulin therapy stimulated protein anabolism in younger but not older patients and failed to prevent atrophy. The insulin- sensitizer glitazones are promising agents against atrophy but the un-favorable benefit/risk profile limits their use. Metformin is an AMPK agonist potentiating insulin actions in the adult human muscle, but not in the aged individuals. The AMPK agonists have the potential to induce atrophy...
2014: Current Diabetes Reviews
David S Fedson
Statins not only reduce levels of LDL-cholesterol, they counteract the inflammatory changes associated with acute coronary syndrome and improve survival. Similarly, in patients hospitalized with laboratory-confirmed seasonal influenza, statin treatment is associated with a 41% reduction in 30-day mortality. Most patients of any age who are at increased risk of influenza mortality have chronic low-grade inflammation characteristic of metabolic syndrome. Moreover, differences in the immune responses of children and adults seem responsible for the low mortality in children and high mortality in adults seen in the 1918 influenza pandemic and in other acute infectious and non-infectious conditions...
September 2013: Antiviral Research
David S Fedson, Steven M Opal
Since December 2011, influenza virologists and biosecurity experts have been engaged in a controversial debate over research on the transmissibility of H5N1 influenza viruses. Influenza virologists disagreed with the NSABB's recommendation not to publish experimental details of their findings, whereas biosecurity experts wanted the details to be withheld and future research restricted. The virologists initially declared a voluntary moratorium on their work, but later the NSABB allowed their articles to be published, and soon transmissibility research will resume...
May 2013: Human Vaccines & Immunotherapeutics
Martina Düfer, Katja Noack, Peter Krippeit-Drews, Gisela Drews
The AMP-activated protein kinase (AMPK) is one of the key players in cellular energy regulation adapting cellular demands to nutritional and metabolic variations. Oral antidiabetic drugs like metformin and glitazones (thiazolidinediones) are known to stimulate this enzyme. Besides their established action on peripheral organs including liver and muscles, it has been claimed that these drugs may affect β-cell function. However, it is still a matter of debate whether pharmacological AMPK stimulation increases or decreases insulin secretion...
May 2010: Islets
Emmanuel Beck, André J Scheen
Type 2 diabetes is associated with a higher risk of cancer, which appears more obvious since the reduction of cardiovascular mortality. All glucose-lowering oral agents do not have the same impact on cancer: the risk is increased with sulfonylureas and decreased with metformin (and glitazones). Numerous epidemiological observational and case-control studies showed that metformin is associated with a lower incidence of cancer and a lower cancer-related death rate. A dose-response relationship and a relation between duration of prior treatment with metformin and the protective effect against cancer have been reported...
September 1, 2010: Revue Médicale Suisse
M Shah, B Kola, A Bataveljic, T R Arnett, B Viollet, L Saxon, M Korbonits, C Chenu
Adenosine 5'-monophosphate-activated protein kinase (AMPK), a regulator of energy homeostasis, has a central role in mediating the appetite-modulating and metabolic effects of many hormones and antidiabetic drugs metformin and glitazones. The objective of this study was to determine if AMPK can be activated in osteoblasts by known AMPK modulators and if AMPK activity is involved in osteoblast function in vitro and regulation of bone mass in vivo. ROS 17/2.8 rat osteoblast-like cells were cultured in the presence of AMPK activators (AICAR and metformin), AMPK inhibitor (compound C), the gastric peptide hormone ghrelin and the beta-adrenergic blocker propranolol...
August 2010: Bone
Ghadeer Za'tara, Jacob Bar-Tana, Bella Kalderon, Marianne Suter, Etedal Morad, Dmitry Samovski, Dietbert Neumann, Rachel Hertz
The antidiabetic efficacy of first-line insulin sensitizers (e.g., metformin, glitazones) is accounted for by activation of AMP-activated protein kinase (AMPK). Long chain fatty acids (LCFA) activate AMPK, but their putative antidiabetic efficacy is masked by their beta-oxidized or esterified lipid products. Substituted alpha,omega-dicarboxylic acids of 14-18 carbon atoms in length (MEDICA analogs) are not metabolized beyond their acyl-CoA thioesters, and may therefore simulate AMPK activation by LCFA while avoiding LCFA turnover into beta-oxidized or esterified lipid products...
November 15, 2008: Biochemical Pharmacology
Raúl A Bastarrachea, Julio C Montero, Ictor Saavedra-Gajardo, Ricardo Cerda-Flores, Anselmo Machado-Domínguez, Anthony G Comuzzie
Current strategies to treat type 2 diabetes (DMT2) include reducing insulin resistance using glitazones, supplementing with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucose absorption with alpha-glucosidase inhibitors. In all of these areas, new generations of molecules with improved efficacy and safety profiles, are being investigated. Promising biological targets are rapidly emerging such as the role of lipotoxicity as a cause of glucometabolic insulin resistance, leading to a host of new molecular drug targets such as AMP-activated protein kinase (AMPK) activators, recombinant adiponectin derivatives, and fatty acid synthase (FAS) inhibitors...
January 2008: Revista Médica de Chile
Francesco Turturro, Robert Oliver, Ellen Friday, Itzhak Nissim, Tomas Welbourne
Troglitazone (Tro) and pioglitazone (Pio) activation of peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-gamma-independent pathways was studied in cell lines derived from porcine renal tubules. PPAR-gamma-dependent activation of PPAR response element-driven luciferase gene expression was observed with Pio at 1 microM but not Tro at 1 microM. On the other hand, PPAR-gamma-independent P-ERK activation was observed with 5 microM Tro but not with Pio (5-20 microM). In addition, Pio (1-10 microM) increased metabolic acid production and activated AMP-activated protein kinase (AMPK) associated with decreased mitochondrial membrane potential, whereas Tro (1-20 microM) did not...
March 2007: American Journal of Physiology. Cell Physiology
Monika Lechleitner
Risk factors for the development of type 2 diabetes mellitus, including weight gain, lack of physical exercise and increasing age, are associated with an impaired mitochondrial function. Clinical studies could demonstrate a reduced mitochondrial activity in non-diabetic but insulin-resistant offsprings of type 2 diabetics. A key enzyme in the regulation of cellular energy supply and thus also in glucose and lipid metabolism is AMP-activated proteinkinase (AMPK). Pharmacological substances, which stimulate AMPK-activity ameliorate insulin resistance induced by free fatty acids...
2004: Acta Medica Austriaca
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