Epidermal growth factor excretion and receptor binding in diabetic rats

Urinary epidermal growth factor (EGF) excretion was calculated as ng EGF per mg creatinine and ng EGF per 24 hr. It was increased 4-9 fold in rats with genetic (BB) or streptozotocin-induced diabetes. It decreased to 2-3 fold control values in insulin-treated animals. In contrast, EGF concentration in serum was lower in diabetic than in control rats (360 +/- 72 vs 524 +/- 150 pg/ml, P .086); EGF level in plasma was unchanged (319 +/- 67 vs 313 +/- 96 pg/ml). In diabetic rats EGF content was increased in submaxillary glands (1018 +/- 259 vs 738 +/- 122 pg/mg protein, P .060) but unchanged in the kidneys (70 +/- 18 vs 65 +/- 6 pg/mg protein in controls). EGF binding to the liver microsomes in diabetic rats was decreased by 30-40% and was not restored by insulin therapy. Binding to the kidneys also showed a tendency to decrease in diabetic animals. The EGF excretion and receptor binding were normal in obese normoglycemic Zucker fa/fa rats. We suggest that hyperglycemia and/or glucosuria may affect EGF synthesis and/or excretion in the kidneys and EGF synthesis or accumulation in the megakaryocytes. The mechanism of decreased EGF receptor binding remains to be clarified.