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Food For Thought: Short-Term Fasting Upregulates Glucose Transporters in Neurons and Endothelial Cells, But Not in Astrocytes

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Abstract

Our group previously reported that 6-h fasting increased both insulin II mRNA expression and insulin level in rat hypothalamus. Given that insulin effects on central glucose metabolism are insufficiently understood, we wanted to examine if the centrally produced insulin affects expression and/or regional distribution of glucose transporters, and glycogen stores in the hypothalamus during short-term fasting. In addition to determining the amount of total and activated insulin receptor, glucose transporters, and glycogen, we also studied distribution of insulin receptors and glucose transporters within the hypothalamus. We found that short-term fasting did not affect the astrocytic 45 kDa GLUT1 isoform, but it significantly increased the amount of endothelial 55 kDa GLUT1, and neuronal GLUT3 in the membrane fractions of hypothalamic proteins. The level of GLUT2 whose presence was detected in neurons, ependymocytes and tanycytes was also elevated. Unlike hepatic glycogen which was decreased, hypothalamic glycogen content was not changed after 6-h fasting. Our findings suggest that neurons may be given a priority over astrocytes in terms of glucose supply even during the initial phase of metabolic response to fasting. Namely, increase in glucose influx into the brain extracellular fluid and neurons by increasing the translocation of GLUT1, and GLUT3 in the cell membrane may represent the first line of defense in times of scarcity. The absence of co-localization of these membrane transporters with the activated insulin receptor suggests this process takes place in an insulin-independent manner.

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Acknowledgements

The authors wish to thank Michael A. Chirillo MD/PhD (Department of Internal Medicine, The University of Utah School of Medicine, Salt Lake City, Utah, USA) for his help with editing and proofreading and Marko Miler PhD (Department of Cytology, Institute for Biological Research “Sinisa Stankovic”, Belgrade, Serbia) for his assistance with histological staining. This study was supported by Ministry of Education, Science and Technological Development, Republic of Serbia (173023).

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This study was supported by Ministry of Education, Science and Technological Development, Republic of Serbia (173023).

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Correspondence to Tamara Dakic.

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All procedures performed in study involving animals were in accordance with the rules of the Federation of European Laboratory Animal Science and the ethical standard of the Faculty of Biology, University of Belgrade and Serbian Ministry of Agriculture, Forestry and Water Management, Veterinary Directorate.

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Dakic, T., Jevdjovic, T., Lakic, I. et al. Food For Thought: Short-Term Fasting Upregulates Glucose Transporters in Neurons and Endothelial Cells, But Not in Astrocytes. Neurochem Res 44, 388–399 (2019). https://doi.org/10.1007/s11064-018-2685-6

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