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. 2018 Mar 16;9:1118. doi: 10.1038/s41467-018-03490-8

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© The Author(s) 2018

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 — Upper small intestinal casein infusion lowers glucose production through activation of PepT1 in healthy rodents. In vivo glucose kinetics were assessed in conscious, unrestrained healthy rats using the pancreatic (basal insulin) euglycemic clamp as outlined in a. Rates of glucose infusion (b), glucose production (GP, c), and glucose uptake (d) in rats that received an upper small intestinal (S.I). infusion of saline (n = 10) or casein (n = 9), intravenous (IV) infusion of casein (n = 5), upper small intestinal infusion of saline+4-AMBA (n = 6), casein+4-APAA (n = 5), or casein+4-AMBA (n = 6). Relative PepT1 mRNA expression in the mucosal layer isolated from S.I. segments ~6–10 cm (upper S.I., e) or ~25–30 cm (mid-S.I., f) distal to the pyloric sphincter in rats that received an upper S.I. lentiviral infection with control mismatch (n = 6) or PepT1 shRNA (n = 6) particles. Rates of glucose production (g) and glucose infusion (h) in rats that received mismatch shRNA lentiviral infection+saline infusion (n = 6), mismatch+casein infusion (n = 6), PepT1 shRNA lentiviral infection+saline infusion (n = 5), or PepT1 shRNA+casein infusion (n = 6). Rates of glucose infusion (i) and glucose production (j) in rats that received saline+the GLP-1 receptor antagonist exendin-9 (n = 3) or casein+exendin-9 (n = 6). Values are presented as mean ± s.e.m., where basal represents the average GP of t = 60–90, clamp represents the average GP of t = 190–200 and asterisk (*) represents p < 0.05 compared to saline control. Statistical significance was determined using an unpaired, two-tailed t-test (two groups) or ANOVA with Tukey post-hoc test (3+ groups)