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. 2017 Jun 5;7:2762. doi: 10.1038/s41598-017-02884-w

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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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Chronic drug treatment led to progressive changes in blood glucose metabolism. Time course (mean ± SEM) of fasting plasma levels of glucose (A), insulin (B) and HOMA-IR (C) during chronic drug treatment. The overall effect of the treatment on glucose (D), insulin (E), and HOMA-IR (F) using time as repeated measure and compared with the baseline on Week 0 of each group. Animals received OLZ, CLZ, or cookie dough alone (control), as indicated. Data represent mean ± SEM (n = 12 per group). *p < 0.05 and **p < 0.01: OLZ treatment vs. control, ^# p < 0.05 and ^## p < 0.01: CLZ treatment vs. control. ^$ p < 0.05, ^$$ p < 0.01, and ^$$$ p < 0.001: OLZ treatment vs. the baseline of OLZ group. ^& p < 0.05 and ^&&& p < 0.001: CLZ treatment vs. the baseline of CLZ group. C: control; O: OLZ; Cl: CLZ.