FIG. 3.

IRS-2–deficient Akita (IRS-2^−/−;Akita) mice demonstrated a decreased β-cell mass and the enhancement of β-cell apoptosis. A: Body weight gain (n = 8–18). *P < 0.05 vs. Akita mice. B: Fed blood glucose levels (n = 8–18). *P < 0.05 and **P < 0.01 vs. Akita mice. C: β-Cell mass (n = 8). The β-cell area is shown as a proportion of the area of the entire pancreas (aged 8 weeks). D: The proportion of TUNEL-positive cells is shown as a percentage of the total number of insulin-positive cells in the sections (aged 8 weeks, n = 8). E–H: Isolated islets of WT (IRS-2^+/+) or IRS-2^−/− mice were incubated with 1 μmol/L thapsigargin (Thaps) or vehicle for 24 h at 2.8, 5.6, or 11.1 mmol/L glucose (E) or at 5.6 mmol/L glucose (F–H). E: mRNA expression levels in the islets (n = 8). F, left: The total cell extracts from the islets were subjected to immunoblotting as indicated. F, right: Intensity of the signals quantified by densitometry (n = 4). G: Flow-cytometric analysis of cleaved caspase-3 levels in islets. Values shown represent the mean fluorescence of normal-sized cells (upper populations of forward scatter [FSC], i.e., viable cells) in the indicated population. The results of one of three independent experiments are shown. H: Number of TUNEL-positive β-cells in the islets (at least 30 islets per indicated group). A GSK-3 inhibitor, 0.5 μmol/L BIO, was added concomitantly with thapsigargin. *P < 0.05. n.s., not significant.