Abstract
Autophagy is a natural process by which a cell maintains homeostasis, usually taking place unnoticed by adjacent cells. Glucose is involved in a negative feedback loop in autophagy. Autophagy is characterized by the induction and secretion of HMGB1, yet the nature of the inflammatory response during and the effect of glucose administration on autophagy are not well understood. Systemic inflammation was induced in experimental animals by LPS injection (7.5 mg/kg) followed by a continuous infusion of either 1%, 5%, or 25% glucose. Autophagy was visualized by immunohistochemistry 12 h after LPS injection. Likewise, protein levels of microtubule-associated protein light chain 3 (LC3)-II, autophagy-related protein 7 (Atg7), and high-mobility group box 1 (HMGB1) were assayed by western blot analysis. We found that autophagy increased in liver tissue in response to LPS-induced systemic inflammation. However, protein levels decreased in rats receiving LPS and a 5% glucose solution. Our results suggest that LPS-induced systemic inflammation increases autophagy in liver cells, potentially involving the upregulation of LC3-II, Atg7, and HMGB1. We also show that a 5% glucose infusion reduces autophagy. We propose that maintaining serum glucose levels with an adequate glucose dose improves systemic inflammation by reducing autophagy.
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Acknowledgments
The authors would like to thank Hiroaki Kawazato and Aiko Yasuda for their helpful advice on the preparation of samples for transmission electron microscopy.
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Institution where the work was performed: Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita 879-5593, Japan
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This work was supported by a Grant-in-Aid program for Science Research (KAKENHI).
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Hagiwara, S., Iwasaka, H., Hasegawa, A. et al. Infusion of a Glucose Solution Reduces Autophagy in the Liver after LPS-induced Systemic Inflammation. Inflammation 35, 249–258 (2012). https://doi.org/10.1007/s10753-011-9311-y
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DOI: https://doi.org/10.1007/s10753-011-9311-y