fosbretabulin and Diabetes-Mellitus--Type-2

Obstetrical complications affect more than a third of women globally, but are underrepresented in clinical research. Little is known about the comprehensive obstetrical clinical trial landscape, how it compares with other fields, or factors associated with the successful completion of obstetrical trials.. This study aimed to characterize obstetrical clinical trials registered on ClinicalTrials.gov with the primary objective of identifying features associated with early discontinuation and results reporting.. This is a cross-sectional study with descriptive, logistic regression and Cox regression analyses of clinical trials registered on ClinicalTrials.gov. Our primary exposure variables were trial focus (obstetrical or nonobstetrical) and trial funding (industry, United States government, or academic). We conducted additional exploratory analyses of other trial features including design, enrollment, and therapeutic focus. We examined the associations of exposure variables and other trial features with 2 primary outcomes: early discontinuation and results reporting.. Obstetrical trials represent only 1.9% of all clinical trials in ClinicalTrials.gov and have comparatively poor completion. All stakeholders should commit to increasing the number of obstetrical trials and improving their completion and dissemination to ensure clinical research reflects the obstetrical burden of disease and advances maternal health.

Topics: Adipose Tissue, White; Adult; Aged; Air Pollutants; Animals; Anti-Inflammatory Agents; Arginine; bcl-2-Associated X Protein; Biofuels; Biological Products; Blood Glucose; Breast Neoplasms; Caspases; CD36 Antigens; Cell Communication; Cell Proliferation; Cell Survival; Cooking; Cross-Sectional Studies; Databases, Factual; Diabetes Mellitus, Type 2; Diphtheria Toxin; Double-Blind Method; Exenatide; Extracellular Polymeric Substance Matrix; Feasibility Studies; Female; Filgrastim; Fruit; Galactose; Gene Deletion; Gene Knockdown Techniques; Glucagon; Glucagon-Like Peptide-1 Receptor; Glucagon-Secreting Cells; Glucose; Glycated Hemoglobin; Hematopoietic Stem Cell Mobilization; Household Articles; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Islets of Langerhans; Lung; Lymphoma; Male; Metals, Heavy; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Nanoparticles; Neoplasms; Obesity; Obstetrics; Odds Ratio; Oxygen; Peripheral Blood Stem Cell Transplantation; Photochemotherapy; Plant Extracts; Polyethylene Glycols; Polyglutamic Acid; Porosity; Postprandial Period; Prospective Studies; Quality of Life; Receptors, Glucagon; Receptors, LDL; Receptors, Somatostatin; Registries; Rhodophyta; Rhodotorula; Risk Factors; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Somatostatin; Stilbenes; Terminalia; Treatment Outcome; United States; Venoms

Resveratrol was reported to increase insulin sensitivity accompanied with the activation of AMP-activated protein kinase (AMPK), which is a key regulator of energy balance and an important drug target for type 2 diabetes. However, the effect of resveratrol structural analogs on AMPK activity and insulin sensitivity is still largely unknown. In this study, we analyzed the effect of several resveratrol structural analogs on AMPK activity in HepG2 cells, and combretastatin A-4 (CA-4) was identified as an activator of AMPK determined by its phosphorylation. AMPK activation was further confirmed by the phosphorylation of downstream acetyl-CoA carboxylase (ACC) and the decrease of upstream ATP level. Further investigation showed that CA-4 activates PPAR transcriptional activity in vitro with the luciferase reporter assay. In addition, we showed that CA-4 activated AMPK and downregulated gluconeogenic enzyme mRNA levels in liver, and improved the fasting blood glucose level in diabetic db/db mice. These results suggested that resveratrol analogs, such as CA-4, can function similarly as resveratrol and may provide important tools for improving insulin sensitivity.

Topics: 3T3-L1 Cells; Acetyl-CoA Carboxylase; Adenosine Triphosphate; AMP-Activated Protein Kinases; Animals; Diabetes Mellitus, Type 2; Enzyme Activation; Glucose; Humans; Mice; Mice, Inbred C57BL; Multienzyme Complexes; Phosphorylation; Poly(ADP-ribose) Polymerases; Protein Serine-Threonine Kinases; Stilbenes