Morphological characterization of systemic changes in KK-Ay mice as an animal model of type 2 diabetes.

ABSTRACT

BACKGROUND: KK-Ay mice, a relevant model of human type 2 diabetes mellitus, are used worldwide for the assessment of pharmacological effects of new anti-diabetes drugs. MATERIALS AND METHODS: KK-Ay mice were examined at five weeks of age (non-hyperglycemic condition) and at 10 and 14 weeks of age (hyperglycemic condition). RESULTS: Islet cell hypertrophy was observed in 10- and 14-week-old mice. The area ratio of islet cells to total pancreas significantly increased compared to that of age-matched C57BL/6J mice. Plasma insulin concentration increased in 14-week-old KK-Ay mice. Enlargement of mesangial matrix and increased glomerular area were seen in kidneys of KK-Ay mice. Fatty changes were observed in the liver. Total plasma cholesterol and triglyceride levels increased compared to that of five-week-old KK-Ay mice. CONCLUSION: The present results on young/adult KK-Ay mice indicate that the hyperglycemic state developing at the early stage of diabetes mellitus is due to related changes in systemic organs.