Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus

Yellow KK mice carrying the 'yellow obese' gene Ay are a well established polygenic model for human non-insulin dependent diabetes mellitus. These animals develop marked adiposity and decreased glucose tolerance relative to their control littermates, KK mice. The authors monitored glucose tolerance in KK-A(y) mice over time and observed a significant (P <= 0.05) age-dependent improvement (13.3% by 175 d of age and 36.4% by 212 d of age, relative to 85 d of age). During the same time period, body weight and food and water consumption were relatively constant. The authors also measured plasma levels of endocrine hormones that are important in diabetes. Levels of insulin were approximately 8 times higher and levels of amylin 3 times higher in 220-d-old KK-A(y) mice than in 180-d-old mice, whereas levels of glucagon-like peptide 1, glucagon and leptin remained relatively constant. These findings suggest that KK-A(y) mice undergo an age-dependent improvement of glucose tolerance when maintained on a normal diet for 25 weeks or longer, due in part to increases in plasma levels of insulin and amylin.