Scientific literature alert: Spatial patterns of hepatocyte glucose flux revealed by stable isotope tracing

Rafael Arrojo E Drigo, Assistant professor, and his team in the Vanderbilt Diabetes Research and Training Center / Vanderbilt University School of Medicine Basic Sciences just published in Nature Communcations on 1st of July a fundamental research on cell metabolism: Spatial patterns of hepatocyte glucose flux revealed by stable isotope tracing (open access).

This study introduces a multi-modal imaging and analysis pipeline to understand glucose metabolism from whole animals to subcellular compartments. Using stable isotope tracing with ¹³C-glucose, the authors combined animal scale mass spectrometry and a correlative microscopy technique called MIMS-EM (Multi-Isotope Imaging Mass Spectrometry with Electron Microscopy). MIMS-EM leverages high-resolution SEM with isotope mapping with the NanoSIMS ion microprobe to visualize ¹³C incorporation from glucose (figure below) into hepatocyte organelles. Machine learning (2D U-Nets) was used to segment mitochondria, ER, lipid droplets, and glycogen depots. Contact between organelles appears linked to their ¹³C enrichment levels and therefore to the glucose uptake. Indeed, glucose influx reorganizes hepatocyte organelle contact networks during glycogenesis. The study reveals that glycogenesis, located in the ¹³C-glucose depots, occurs near lipid droplets scaffold in hepatocyte cell. This work establishes MIMS-EM as a powerful tool for spatially resolved metabolic analysis at nanometer scale.