RENAL INSULIN-LIKE GROWTH FACTOR-I AND GROWTH-HORMONE RECEPTOR-BINDING IN EXPERIMENTAL DIABETES AND AFTER UNILATERAL NEPHRECTOMY IN THE RAT

We have measured specific binding of insulin-like growth factor I and growth hormone to renal plasma membranes from control, streptozotocin-diabetic, insulin-treated diabetic, uninephrectomised and combined diabetic-uninephrectomised male Wistar rats. Control, insulin-treated and uninephrectomised rats had similar body weights after 7 days (243 +/- 2 g), whereas diabetic and diabetic-uninephrectomised animals were significantly lighter (219 +/- 4 and 203 +/- 4 g, p < 0.05). Blood glucose concentrations were similar in the diabetic and diabetic-uninephrectomised animals (around 26 mmol/l) but significantly lower in the insulin-treated group. Right kidney weight increased by 14% in the control, insulin-treated and sham-nephrectomised animals, by 33% in the diabetic group, 38% in the nephrectomised animals and 60% in the diabetic-nephrectomised group. The renal content of insulin-like growth factor I was similar and stable in the control, insulin-treated and sham-nephrectomised animals (208 +/- 14 ng/g wet weight) but rose to a peak of 669 +/- 35 ng/g in the diabetic group (p < 0.001), 871 +/- 34 ng/g in the nephrectomised animals (p < 0.001) and 1012 +/- 43 ng/g in the diabetic-uninephrectomised group (p < 0.001). Maximum binding of insulin-like growth factor I fell on day 1 in the diabetic group (8.3 +/- 1.4 vs 5.2 +/- 0.71 x 10(-11) mol/l; p < 0.01) but thereafter was identical to control animals. In the insulin-treated animals, maximum binding rose to 11.0 +/- 1.1 x 10(-11) mol/l, significantly different from control and diabetic animals (p < 0.01). Growth hormone binding fell acutely in both the diabetic and diabetic-nephrectomised animals (3.13 +/- 0.58 and 2.83 +/- 0.21 vs 7.77 +/- 0.68 x 10(-12) mol/l; p < 0.001 for both). Following uninephrectomy, maximum binding of insulin-like growth factor I and growth hormone was unchanged from control values. We conclude that the rise in renal content of insulin-like growth factor I which precedes the compensatory growth seen after induction of diabetes and uninephrectomy is not due to alterations in insulin-like growth factor I receptor binding and is independent of growth hormone binding.