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 2
Failure of compensatory β cell hyperplasia in HF diet–fed Gck^+/– mice caused by decreased β cell replication rate. (A) Histologic analysis of pancreatic islets of wild-type and Gck^+/– mice after 20 weeks on standard chow or HF diet. Sections were double stained with anti-insulin antibody and a cocktail of anti-glucagon, anti-somatostatin, and anti-pancreatic polypeptide antibodies. Representative islets are shown. Red stain, β cells; brown stain, non–β cells. Scale bars: 100 μm. (B) Quantitation of β cell and non–β cell mass in wild-type and Gck^+/– mice after 20 weeks on standard chow or HF diet. Areas of β or non–β cells (α, δ, and pancreatic polypeptide cells) are shown relative to total pancreas area (n = 4). (C) Changes in β cell mass on HF diet. Shown is β cell area relative to pancreas area (n = 4) after 4, 20, and 40 weeks on HF diet. (D) Number of cells in wild-type and Gck^+/– mouse islets after 20 weeks on standard chow or HF diet (n = 6). (E and F) Replication rate of β cells, assayed (E) on the basis of BrdU incorporation after 20 weeks on standard chow or HF diet or (F) by PCNA staining after 20 weeks on HF diet. Results are shown as ratios of double-positive cells to insulin-positive cells (n = 4). Values represent mean ± SEM. *P < 0.05; **P < 0.01.