OCTREOTIDE PREVENTS THE EARLY INCREASE IN RENAL INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEIN-1 IN STREPTOZOTOCIN-DIABETIC RATS

The early renal growth in streptozotocin (STZ)-induced diabetic rats i s preceded by a transient rise in renal tissue insulin-like growth fac tor (IGF)-I concentration. Administration of the long-acting somatosta tin analog octreotide to STZ diabetic rats inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting met abolic control. we studied the effects of octreotide treatment on the intrarenal IGF axis at 2 and at 7 days after the induction of STZ diab etes. Two days after induction of diabetes, kidney IGF-I was increased from 850 +/- 43 ng/g tissue in controls to 1,648 +/- 165 ng/g tissue (P < 0.001) in diabetic animals. The diabetes-associated increase in r enal IGF-I 48 h after STZ injection was totally prevented by octreotid e (IGF = 780 +/- 57 ng/g tissue), However, 7 days after the induction of diabetes, kidney IGF-I was similar to that of control and was not a ffected by octreotide. No difference in serum IGF-I was observed betwe en controls and diabetic rats after 2 days of diabetes; however, octre otide treatment resulted in a significant decrease of serum IGF-I afte r 2 days when compared with control rats (P < 0.05). Renal IGF-I mRNA was significantly decreased to the same extent in both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I recep tor (IGF-IR) mRNA was unchanged in rats from either group. Two days af ter induction of diabetes, renal insulin-like growth factor binding pr otein (IGFBP)-1 mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared with controls. Octreotide treatment prevented the diabetes-associated rise in renal IGFBP-1 mRNA and protein. However, 7 days after the indu ction of diabetes, renal IGFBP-1 mRNA and protein were similarly incre ased in both octreotide-treated or untreated diabetic rats. Renal IGFB P-3 gene expression and protein and 1GFPB-5 mRNA remained unchanged af ter 2 and 7 days of diabetes when treated or untreated with octreotide . We conclude that the well-known inhibitory effect of octreotide on t he early increase in renal IGF-I concentration and renal size in diabe tes may be mediated through a direct effect on renal IGFBP-1 levels.