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. 2017 Nov 21;8:1658. doi: 10.1038/s41467-017-01863-z

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© The Author(s) 2017

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. 3 — The SeP-neutralizing Ab improved glucose metabolism impaired by excess SeP. a, b Neutralizing mAb AE2 improved glucose tolerance impaired by human SeP administration in vivo. After the administration of AE2 and hSeP following the scheme of Supplementary Fig. 4a, glucose (1.5 g/kg) was administered, and then blood glucose was determined (a, n = 6–8, means ± s.e.m.). Open triangle, PBS/control IgG; green square, PBS/AE2; red circle, hSeP(+)/control IgG; blue circle, hSeP(+)/AE2. **P < 0.01, when compared hSeP(+)/control IgG group with other groups, Tukey-ANOVA. Area under the curve for blood glucose levels is shown in b (n = 6–8, means ± s.e.m.). *P < 0.05, Student's t-test. c–e Neutralizing mAb AE2 improved insulin resistance impaired by SeP administration in vivo. After the administration of AE2 and hSeP following the scheme shown in Supplementary Fig. 4a, insulin (0.5 U/kg) was administered, and blood glucose was determined (c, n = 5–8, means ± s.e.m.). **P < 0.01, ***P < 0.001, Tukey-ANOVA. Area under the curve for blood glucose levels is shown in d (n = 5–8, means ± s.e.m.). ***P < 0.001, Student's t-test. Effect of AE2 mAb administration on phosphorylation of insulin receptor (IR) and Akt in skeletal muscle (e). In AE2- and hSeP-treated mice, muscle tissues were excised 15 min after insulin administration (0.5 U/kg), and analysed by western blotting (n = 5–8, means ± s.e.m.). *P < 0.05, Student's t-test. f Blood insulin levels were significantly decreased by human SeP administration. Blood insulin levels were determined 2 h after second hSeP or PBS administration under feeding conditions (n = 5, means ± s.e.m.). **P < 0.01, Student's t-test. g Blood insulin levels were significantly increased by AE2 administration under feeding conditions (n = 5, means ± s.e.m.). *P < 0.05, **P < 0.01, Tukey-ANOVA. h Blood insulin levels were significantly increased during a glucose-tolerance test. At each designated time, blood insulin was determined (n = 7–8, means ± s.e.m.). *P < 0.05, **P < 0.01, Tukey-ANOVA (c, h). Closed circle, hSeP(+)/control IgG; open circle, hSeP(+)/AE2