Fig 8. Diabetic mice display a decrease in expression of endocytic proteins associated with alterations in their urinary shedding.

Diabetic and control mice kidneys were removed five weeks after stz injection. Western blotting to investigate the expression of albumin receptors megalin and cubilin and downstream Akt substrate was performed. Diabetic mice had downregulation of megalin, cubilin and AS160 expression in their kidney (A). Mice injected with stz to induce T1D and control animals underwent 24hr urine collection in metabolic cages 3 and 5 weeks after stz injection. Urinary proteins were precipitated and examined for megalin and cubilin expression. Urinary shedding of megalin was diminished whereas cubilin shedding was evident in diabetic mice at 3 weeks after stz injection at the time of minimal MA (A). At 3 weeks diabetic mice had minimal MA. A significant increase in MA was observed at 5 weeks after stz injection. Increase in urinary albumin excretion in diabetic mice was confirmed by Coomassie staining (B). Densitometric measurement of western blotting of megalin, cubilin and AS160 adjusted for β-actin revealed a statistically significant decrease in expression of these proteins in stz injected diabetic mice (C) *: p<0.05.