title: Visualization and quantification of cerebral metabolic fluxes of glucose in awake mice.
abstract: Biotransformation of glucose in organs includes multiple pathways, while quantitative evaluation of percentages of its utilization for individual pathways and their spatial heterogeneity in vivo remain unknown. Imaging MS (IMS) and metabolomics combined with a focused microwave irradiation for rapidly fixing tissue metabolism allowed us to quantify and visualize metabolic fluxes of glucose-derived metabolites in the mouse brain in vivo. At 15 min after the intraperitoneal injection of (13) C6 -labeled glucose, the mouse brain was exposed to focused microwave irradiation, which can stop brain metabolism within 1 s. Quantification of metabolic intermediates containing (13) C atoms revealed that a majority of the (13) C6 -glucose was diverted into syntheses of glutamate, lactate, and uridine diphosphate (UDP)-glucose. IMS showed that regions rich in glutaminergic neurons exhibited a large signal of (13) C2 -labeled glutamate. On the other hand, the midbrain region was enriched with an intensive (13) C6 -labeled UDP-glucose signal, suggesting an active glycogen synthesis. Collectively, application of the current method makes it possible to examine the fluxes of glucose metabolism in a region-specific manner.
authors: Department of Biochemistry, School of Medicine, Keio University, Tokyo, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PRESTO) Project, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Sugiura
authors: Kurara
authors: K
authors: Honda
authors: Mayumi
authors: M
authors: Kajimura
authors: Makoto
authors: M
authors: Suematsu
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes / Q000737:chemistry; D016371:Cranial Irradiation; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D009682:Magnetic Resonance Spectroscopy; D008636:Mesencephalon / Q000378:metabolism / Q000528:radiation effects; D055432:Metabolomics; D051379:Mice; D008872:Microwaves; D009474:Neurons / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D002250:Carbon Radioisotopes; D018698:Glutamic Acid; D006003:Glycogen; D005947:Glucose
keywords: Focused microwave irradiation; MALDI-imaging mass spectrometry; Metabolic flux; Stable isotope; Technology