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The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.
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http://dx.doi.org/10.1016/j.bmcl.2020.127760 | DOI Listing |
Diabetes
September 2025
Institute for Physical Activity and Nutrition, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Victoria, Australia.
Unlabelled: Despite stimulating glucagon secretion, the mechanisms by which protein ingestion lowers glucose excursions remain unclear. We investigated this using the triple stable isotope glucose tracer technique to measure postprandial glucose fluxes. Eleven healthy adults completed three trials, ingesting 25 g glucose (25G; 100 kcal), 50 g glucose (50G; 200 kcal), or 25 g glucose plus 25 g whey protein (25WG; 200 kcal).
View Article and Find Full Text PDFExp Ther Med
November 2025
Department of Obstetrics and Gynecology, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu 226007, P.R. China.
Gestational diabetes mellitus (GDM), a type of diabetes mellitus occurring in pregnant women, increases the risk of birth trauma. Solute carrier family 2 member 4 (SLC2A4) polymorphism is notably associated with GDM susceptibility; however, the mechanism is unknown. In the present study, HTR-8/SVneo cells were treated with high glucose concentrations and transfected with SLC2A4 and Forkhead box O (FoxO)1 to investigate their roles in the insulin (INS) resistance of GDM trophoblast cells.
View Article and Find Full Text PDFFEBS Lett
September 2025
Kusuma School of Biological Sciences, Indian Institute of Technology-Delhi, Hauz Khas, New Delhi, India.
Neuronal insulin signaling is essential for regulating glucose metabolism and cognitive functions in the brain. Disruptions cause neuronal insulin resistance, potentially causing type 2 diabetes (T2D) and Alzheimer's disease (AD). Therefore, we investigated alternative pathways that maintain glucose homeostasis beyond traditional insulin signaling.
View Article and Find Full Text PDFDiabetes Obes Metab
September 2025
Turku PET Centre, University of Turku, Turku, Finland.
Aims: Obesity is associated with increased insulin-stimulated brain glucose uptake (BGU) which is opposite to decreased GU observed in peripheral tissues. Increased BGU was shown to be reversed by weight loss and exercise training, but the mechanisms remain unknown. We investigated whether neuroinflammation (TSPO availability) and brain activity drive the obesity-associated increase in BGU and whether this increase is reversed by exercise training.
View Article and Find Full Text PDFNucl Med Biol
August 2025
Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
Background: Glutamine is an important metabolic substrate in many aggressive tumors, with comparable importance to glucose metabolism. Utilizing human breast cancer mouse xenograft models, we studied the kinetics of the PET imaging agent, L-5-[C]-glutamine ([C]glutamine or [C]GLN) a biochemical authentic substrate for glutamine metabolism, to further characterize the metabolism of glutamine and downstream labeled metabolites. Studies were performed with and without inhibition of the enzyme, glutaminase (GLS), the first step in glutamine catabolism that generates glutamate, and key target for therapy directed to glutamine-metabolizing cancers.
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