There is a growing body of evidence that the formation and accumulation of
advanced glycation end products (AGE) have been known to progress under diabetic conditions, thereby being involved in
diabetic vascular complications. Further, we, along with others, have recently found AGE could disturb
insulin actions in cultured adipocytes and skeletal muscles. However, the pathological role of AGE in
insulin resistance in vivo is not fully understood. Therefore, in this study, we examined whether
pyridoxamine, an inhibitor of AGE formation could ameliorate
insulin resistance in KK-A(y) mice, a model animal of obese,
type 2 diabetes. Fasting
blood glucose, serum levels of
insulin and AGE in KK-A(y) mice were elevated as the mice got older (from 5 weeks old to 15 weeks old). Serum levels of AGE were positively correlated with
insulin (R(2)=0.3956, P=0.002) in KK-A(y) mice. Administration of
pyridoxamine dose-dependently decreased fasting
insulin levels and improved
insulin sensitivity in KK-A(y) mice of 10 weeks old, although it did not affect fasting
blood glucose levels. Our present study suggests the involvement of AGE in
insulin resistance in KK-A(y) mice. Inhibition of AGE formation may be a novel therapeutic target for improving
insulin resistance in diabetes with
obesity.