Glucokinase and IRS-2 are required for compensatory β cell hyperplasia in response to high-fat diet–induced insulin resistance
J. Clin. Invest. Yasuo Terauchi, et al. 117:246 doi:10.1172/JCI17645 [Go to this article.]

Figure 6
Transgenic rescue by crossing Gck^+/– mice with βIrs2Tg mice. (A and B) Glucose tolerance in wild-type, Gck^+/–, βIrs2Tg, and βIrs2TgGck^+/– mice after 20 weeks on HF diet. (A) Plasma glucose levels. (B) Serum insulin levels. n = 31 (wild-type), 20 (βIrs2Tg), 35 (Gck^+/–), 16 (βIrs2TgGck^+/–). *P < 0.05, Gck^+/– versus βIrs2TgGck^+/–. (C) Histologic analysis of wild-type, Gck^+/–, βIrs2Tg, and βIrs2TgGck^+/– mouse islets after 20 weeks on HF diet. Representative pancreatic islets are shown. Top panels show insulin staining; bottom panels show BrdU staining. Scale bars: 100 μm. Original magnification, ×100 (top panels); ×400 (bottom panels). (D) Area of β cells in each islet after 20 weeks on HF diet. We examined 100–150 islets from 3 animals per group. (E) Replication rate of β cells, assayed on the basis of BrdU incorporation after 20 weeks on HF diet. Results are shown as ratios of insulin and BrdU double-positive cells to insulin-positive cells (n = 4). (F) Static incubation study of islets after 20 weeks on the HF diet. Static incubation of 10 islets/tube was performed at 37°C for 1 hour with various glucose concentrations after preincubation with a 2.8-mM glucose concentration for 20 minutes. Results are shown as pg insulin/cell/h (n = 4). Values represent mean ± SEM. *P < 0.05; **P < 0.01.