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. 2023 Nov 9;20(5):566–576. doi: 10.1038/s41589-023-01466-4

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© The Author(s) 2023

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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Extended Data Fig. 3 — (a) IPGTT of 8–12 weeks old male chow-fed CD-1/ICR vehicle- or 12 mg/kg AZD7762-treated mice. P-value: 15 min, p = 1.00E-05; 30 min, p = 8.00E-06; 60 min, p = 0.006. n = 20 (vehicle); n = 14 (AZD7762). (b) GSIS of chow-fed 8–12 weeks old male CD-1/ICR vehicle- or 12 mg/kg AZD7762-treated mice. P-value: 0 min, p = 0.002; 15 min, p = 0.017. n = 25 (vehicle); n = 32 (AZD7762). (c) Glucose levels of chow-fed 8–12 weeks old male CD-1/ICR vehicle- or 12 mg/kg AZD7762-treated mice without glucose injection. n = 8 (vehicle); n = 7 (AZD7762). (d) IPGTT of 8–12 weeks old male chow-fed CD-1/ICR vehicle- or 12 mg/kg AZD7762-treated mice 24 hours before the experiment. n = 8 (vehicle); n = 7 (AZD7762). (e) HOMA-IR of vehicle- or 25 mg/kg AZD7762-treated mice. Left: 8–12 weeks old male chow-fed CD-1/ICR mice. n = 10 mice per group. Right: 16-week-old male obese ob/ob vehicle- or 25 mg/kg AZD7762-treated mice. n = 9 mice per group. (f) Active GLP-1 levels during IPGTT of chow-fed 8–12 weeks old male CD-1/ICR vehicle- or 12 mg/kg AZD7762-treated mice. n = 11(vehicle); n = 12 (AZD7762). (g) Total GIP levels during IPGTT of chow-fed 8–12 weeks old male CD-1/ICR vehicle- or 12 mg/kg AZD7762-treated mice. P-value: 0 min, p = 0.008; 15 min, p = 0.001. n = 15 (vehicle); n = 12 (AZD7762). (h) SST secretion during GSIS of intact mouse islets with control or 1 µM AZD7762. n = 4 biological replicates. (i) glucagon secretion during GSIS of intact mouse islets in the with control or 1 µM AZD7762. n = 4 biological replicates. (j) Glucose levels during insulin tolerance test of 8-month-old male chow-fed wildtype and Chk2^−/− mice. n = 4 (wildtype), n = 5 (Chk2^−/−). Mice were fasted overnight for GTT and GSIS experiments. Data represent the Mean ± SEM. For a-e & h-i, P-value were calculated by two-sided Student’s t-test. Statistical significance *p < 0.05, **p < 0.01, n.s. for not significantly different.

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