THE EFFECT OF LOW-DOSE OCTREOTIDE ADMINISTRATION ON RENAL-FUNCTION AND ON GENE-EXPRESSION OF IGF-I AXIS COMPONENTS IN EXPERIMENTAL DIABETES-MELLITUS

The present study was undertaken to assess the chronic effects of low dose octreotide (Oc) administration in rats with experimental diabetes mellitus (DM). Metabolic and clearance studies were performed in cont rol normal rats, in rats with streptozotocin-induced DM of 1 week dura tion and in similar DM rats treated with Oc, 10-20 mu g/day. Gene expr ession of IGF-I, IGF-I receptor (IGF-I R) and IGF-binding protein-1 (I GFBP-1) was examined in renal tissue from normal DM animals and DM ani mals treated with Oc 10, 20 and 100 mu g/day. Seven days of Oc adminis tration, 10 mu g/day, in rats with experimental DM, was associated wit h enhanced hyperglycemia, increased glomerular filtration rate and uri nary sodium excretion as compared with untreated DM animals. After a h igher Oc dose, 20 mu g/day, however, there were no significant changes in renal function and in glycemic control. Significant increases in k idney weight and kidney weight/body weight ratio were seen in DM rats as compared with control intact animals. These changes were not affect ed by Oc therapy in various doses. Induction of DM was associated with a marked increase in renal IGFBP-1 mRNA expression. There were no sig nificant changes in the expression of IGF-I or IGF-I R mRNA, Oc therap y in a low or high dose did not affect gene expression of IGF-I, IGF-I R or IGFBP-1. Thus, the response to chronic low dose Oc administratio n of DM rats may vary from enhanced hyperglycemia and hyperfiltration to a lack of change in renal function or in glycemic control. Low dose Oc therapy was not associated with significant variations in renal ma ss or in the gene expression of IGF-I axis components. These findings are at variance with previously published studies which show a suppres sive effect of Oc on renal function and growth in experimental diabete s. This apparent discrepancy may be related to the duration oi treatme nt or to a biphasic physiological effect of Oc when used in different doses.