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The development of proteinuria and its response to insulin therapy in acute experimental diabetes was examined in 11 female rats by sequentially measuring 24 h excretion of glucose and total protein before diabetes, during 5-37 days of acute streptozotocin diabetes, during and after 7-14 days of continuous subcutaneous insulin administration. Induction of diabetes promptly resulted in marked polyuria (78 +/- 9 ml/24 h), and glycosuria (6.6 +/- 0.7 g/24 h), while proteinuria quadrupled (from 4.7 +/- 0.7 to 18.8 +/- 1.8 mg/24 h, p less than 0.001). Concurrent with amelioration of polyuria and glycosuria by insulin treatment, proteinuria decreased strikingly (8.5 +/- 1.2 mg/24 h, p less than 0.001) Polyuria and glycosuria resumed after discontinuing continuous subcutaneous insulin, and proteinuria promptly returned to pretreatment levels (19.0 +/- 2.5 mg/24 h). Similarly decreased proteinuria (8.8 +/- 0.9 mg/24 h) recurred in five rats retreated with insulin after 100 days of diabetes. Elevated proteinuria was not associated with lysozymuria or consistent changes in glomerular filtration rate. The rapid fluctuations in proteinuria attending acute diabetes and its effective treatment suggest that metabolic aberrations of diabetes may directly effect renal handling of proteins.

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