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. 2019 Feb 12;10:714. doi: 10.1038/s41467-019-08582-7

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Inhibition of upper small intestinal mTOR activates a gut–brain axis to lower hepatic glucose production. a Schematic representation of working hypothesis. b, c Glucose infusion rate (b) and glucose production (c) during the clamps in HFD rats infected with upper small intestinal Ad-ca-mTOR and infused with upper intestinal A769662 or saline. ***p < 0.001 vs. saline; determined by unpaired t-test (n = 6 for each group). d, e Quantitative analysis and representative western blot of phosphorylated ACC (d) and raptor (e) protein expression in the upper intestinal mucosa of Ad-ca-mTOR infected HFD rats infused with upper intestinal saline or A769662. Actin, loading control. *p < 0.05 vs. saline as calculated by unpaired t-test (n = 5 for saline, and 6 for A769662 in ACC, and 6/group in raptor). f Western blot of phosphorylated AMPK protein expression in the upper small intestinal mucosa of HFD rats infused with upper intestinal saline or rapamycin. Actin, loading control. *p < 0.05 vs. saline as calculated by unpaired t-test (n = 6 for each group). g, h Glucose infusion rate (g) and glucose production (h) during clamps in HFD rats infused with upper small intestinal saline (n = 7), rapamycin (n = 7), tetracaine (n = 5), rapamycin + tetracaine (n = 6), rapamycin + sham (n = 5) or hepatic vagal branch vagotomy (HVAG) (n = 5). **p < 0.01 or ***p < 0.001 vs. saline, tetracaine, tetracaine + rapamycin, and HVAG + rapamycin; determined by ANOVA with Tukey’s post hoc test. Values are shown as mean ± s.e.m.