Fig. 2 HHKO mice exhibit improved glucose tolerance by increasing plasma incretin levels and insulin secretion. HHKO mice exhibit improved glucose tolerance.

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Fig. 2 HHKO mice exhibit improved glucose tolerance by increasing plasma incretin levels and insulin secretion. HHKO mice exhibit improved glucose tolerance by increasing plasma incretin levels and insulin secretion. (A to C) Plasma insulin (B) and C-peptide (C) levels during OGTT in Fig. 1H mice were used for calculating HOMA-%β (A). #P < 0.05, *P < 0.05 versus WT counterparts. (D to F) Pancreas mass (D), pancreatic insulin content (E), and overall β cell mass (F) were measured in NCD and/or HFD WT and HHKO mice. n = 6 NCD WT, 4 NCD HHKO, 11 HFD WT, and 8 HFD HHKO mice. (G) Plasma insulin/C-peptide ratio in Fig. 1H mice. (H) IPGTTs. n = 11 and 10 per group. (I and J) Plasma total (I, left) and active GLP-1 (I, right) and active GIP (J) levels in 6-hour–fasted HFD WT and HHKO mice before or 10 min after glucose oral gavage (n = 5 and 7 mice per group). *P < 0.05 versus WT controls. (K) OGTTs in HFD mice conducted 30 min after saline or ex9 administration. n = 11 and 10 per group. *P < 0.05, HFD WT + saline versus HFD HHKO + saline. (L and M) Glucagon (Gcg) tolerance tests with (M) or without (L) ex9 administration 30 min before glucagon injection. n = 6 and 7 per group. *P < 0.05. (N) Fasting (6 hours) serum glucagon levels (n = 6, 10, and 8 mice per group). *P < 0.05 versus lane 1. (O) Gluconeogenesis activity assays in primary hepatocytes. n = 5 wells per group. §P < 0.05 versus NCD group in lane 2, *P < 0.05 versus HFD group in lane 1, #P < 0.05 versus HFD group in lane 2. (P) Schematic representation of the experimental procedures for hyperglycemic clamp studies in (Q) to (T). (Q to T) Hyperglycemic clamp studies. Basal HGP (Q), glucose infusion rate (GIR) (R), clamped HGP (S), and %suppression of HGP (T) were calculated as described in Materials and Methods. n = 5, 4, 9, and 7 mice per group. *P < 0.05 versus lane 2, #P < 0.05 versus lane 1, ##P < 0.01 versus lane 1. For statistical analysis, one-way (A, N, O, and R to T) or two-way (B, C, I, J, and L) ANOVA with post hoc t tests between the individual groups was performed. All data are presented as means ± SEM. Yun Sok Lee et al. Sci Adv 2019;5:eaaw4176 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).