Figure 4 .

Metformin decreases the catalytic activity of SHIP2 in db/db mice. A, B) Metformin decreases the catalytic activity of SHIP2 in skeletal muscle (A) and kidney (B) of db/db mice. SHIP2 was immunoprecipitated from tissue lysates and its catalytic activity measured by malachite green phosphate assay (n = 6–8). C–E) Twelve d metformin treatment has no effect on body weight (C), urinary albumin excretion (D), and fasting blood glucose (E) in db/db mice (n = 7–8). F, G) Metformin improves insulin sensitivity of db/db mice. Insulin tolerance test was performed and blood glucose measured at the indicated times after insulin injection, and the area under the curve (AUC) was calculated (n = 5–6). Data are presented as the mean ± sem. *P ≤ 0.05, **P ≤ 0.01 (Student’s t test).