EFFECT OF INSULIN ON WATER AND UREA TRANSPORT IN THE INNER MEDULLARY COLLECTING DUCT

The effect of insulin on water and urea transport was examined in normal isolated rat inner medullary collecting duct (IMCD). Hydraulic conductivity (L(p), x 10(-6) cm.atm(-1).s(-1)), diffusional water permeability (P-dw X 10(-5) cm/s) and [C-14]urea permeability (x 10(-5) cm/s) were studied at 37 degrees C and pH 7.4. Insulin (6 x 10(-8) M; 200 mu U/ml) added to the bath fluid enhanced L(p) from 0.40 +/- 0.10 to 1.21 +/- 1.40 (P < 0.01) and P-dw from 42.40 +/- 3.40 to 58.50 +/- 5.00 (P < 0.02) and also stimulated L(p) in a dose-dependent manner. In the presence of antidiuretic hormone (ADH)-stimulated P-dw (10 mu U/ml), insulin increased P-dw even more. Prostaglandin E(2) (10(-5) M) added to the bath reversibly increased insulin-induced L(p). Forskolin (10(-4) M) blocked the action of insulin. Colchicine (10(-4) M) and V-1- receptor antagonist (10(-4) M) inhibited the development but not the maintenance of insulin-stimulated P-dw. Vanadate (2.5 x 10(-6) M) enhanced P-dw. Polymyxin B (10(-5) M) inhibited the insulin-stimulated P-dw, whereas in a glucose-free medium insulin did not enhance P-dw. Urea transport was not affected by insulin. These data suggest that insulin may enhance water transport, probably by stimulating glucose transporters, which would serve as a water channel. We cannot rule out the possibility that insulin may be eliciting existing ADH-Like mechanisms of water transport, beyond the microtubule step, to establish water transport.