EFFECT OF INSULIN-LIKE GROWTH FACTOR-I INFUSION ON RENAL HYPERTROPHY IN EXPERIMENTAL DIABETES-MELLITUS IN RATS

Initial diabetic renal hypertrophy is preceded by a transient increase in kidney insulin-like growth factor I suggesting that insulin-like growth factor I may be implicated in diabetic kidney growth. The present study was undertaken to examine the effects of exogenous insulin-like growth factor I infusion on diabetic renal hypertrophy at a time when renal insulin-like growth factor I concentration had returned to normal and the initial steep kidney growth rate had diminished to a much slower rate. Groups of rats with diabetes duration of 5 days were infused s. c. for 4 subsequent days with equimolar concentrations of insulin-like growth factor I (36 nmol/day) or insulin (35 nmol/day). Insulin infusion lowered blood glucose to a normal level within 2 days and induced an average body-weight gain of 9.3 +/- 0.6 g/day. Insulin-like growth factor I infused diabetic rats maintained the original diabetic state with blood glucose levels comparable to those of 0.154 mol/l NaCl-infused diabetic rats, but had nevertheless an average body-weight gain of 6.8 +/- 1.0 g/day while untreated diabetic rats had a lower body-weight gain amounting to 3.3 +/- 0.8 g/day (p < 0.01). The kidney weight at day 9 in untreated diabetic animals was about 25 % greater than that of non-diabetic control animals, while in insulin-like growth factor I treated diabetic rats a further increase (p < 0.05) was seen, amounting to 36 % above control level. No increase was seen in the insulin-treated diabetic group. Whole kidney protein, RNA and DNA estimations indicated that, in 0.154 mol/l NaCl-infused diabetic animals, the kidney growth after 9 days constituted a mixture of cellular hypertrophy and hyperplasia while the excess kidney weight increase obtained in insulin-like growth factor I infused diabetic rats was due mainly to hypertrophy. The kidney content of immunoreactive insulin-like growth factor I at day 9 in insulin-like growth factor I infused diabetic rats was on average 85% greater than in 0.154 mol/l NaCl-infused diabetic and non-diabetic control groups, while no differences were found in insulin-like growth factor I mRNA levels. In conclusion, insulin-like growth factor I administration initiated after 5 days of diabetes, with restoration of high kidney insulin-like growth factor I levels similar to those seen after 1-2 days of diabetes, accelerates renal growth, supporting the concept that the early kidney insulin-like growth factor I accumulation may be the stimulus for initial diabetic kidney hypertrophy.