FIG. 1.

Old mice failed to compensate diet-induced insulin resistance and developed diabetes after an 8-week high-fat diet. Young (6-week-old) and old (7-month-old) mice were fed normal diet (ND; 12.2% calories from fat) or high-fat diet (HFD; 55% calories from fat) for 8 weeks. A: Insulin tolerance test in young and old mice after 8 weeks of high-fat diet or normal diet (n = 6 in each group). Mice were fasted 6 h before testing. High-fat diet–fed mice were compared with normal diet–fed mice. **P < 0.005 (60 min). B: Glucose tolerance test in young and old mice after 8 weeks of high-fat diet or normal diet feeding. Mice were fasted overnight, and the blood glucose level was measured before and after glucose challenge. **P < 0.005. C: Blood glucose levels after overnight fasting. High-fat diet–fed mice were compared with normal diet–fed mice. **P < 0.005. D: Analysis of β-cell mass of young and old mice after 8 weeks of normal diet or high-fat diet feeding. Values are representative of 5–6 slides spanning the whole pancreas of each mouse and three mice per group. **P < 0.005.