The early pathological changes of KKAy mice with type 2 diabetes / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the early pathological changes of KKAy mouse model of type 2 diabetes.</p><p><b>METHODS</b>Five male KKAy mice and six C57BL mice each were studied at the age of 8, 16, 20 and 24 weeks. With each mouse a 24-hour urine collection was made for the tests of proteinuria. Plasma insulin, lipids, serum creatinine and urea were also measured. Renal tissues were observed to assess glomerular and tubulointerstial pathology.</p><p><b>RESULTS</b>The KKAy mice developed hyperglycemia, hyperinsulinemia and obesity by 16 weeks of age (P < 0.01). The proteinuria increased with the increasing of age (P < 0.005), but there were no changes in control. The glomerular hypertrophy was observed in KKAy mice at the age of 16 weeks. Computer map analysis system (CMIAS) indicated the expansion of mesangial matrix in KKAy mice with ageing. There was significant tubular dilation, accompanied with focal tubular atrophy and interstitial fibrosis. On electron microscopy, GBM undergo progressive thickening (P < 0.01), accompanied with podocytes fusion and increasing of proteinuria.</p><p><b>CONCLUSIONS</b>KKAy mice developed hyperglycemia, hyperinsulinemia and obesity after 16 weeks, with proteinuria, mesangial matrix accumulation, GBM thickening and tubular dilation. It was considered a good animal model for the early pathology changes of DN.</p>