The effect of low dose octreotide administration on renal function and on gene expression of IGF-I axis components in experimental diabetes mellitus

Abstract

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 control normal rats, in rats with streptozotocin-induced DM of 1 week duration and in similar DM rats treated with Oc, 10-20 µg/day. Gene expression of IGF-I, IGF-I receptor (IGF-I R) and IGF-binding protein-1 (IGFBP-1) was examined in renal tissue from normal DM animals and DM animals treated with Oc 10, 20 and 100 µg/day.Seven days of Oc administration, 10 µg/day, in rats with experimental DM, was associated with enhanced hyperglycemia, increased glomerular filtration rate and urinary sodium excretion as compared with untreated DM animals. After a higher Oc dose, 20 µg/day, however, there were no significant changes in renal function and in glycemic control. Significant increases in kidney weight and kidney weight/body weight ratio were seen in DM rats as compared with control intact animals. These changes were not affected by Oc therapy in various doses.Induction of DM was associated with a marked increase in renal IGFBP-1 mRNA expression. There were no significant changes in the expression of IGF-I or IGF-I R mRNA. Oc therapy 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 administration 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 mass or in the gene expression of IGF-I axis components.These findings are at variance with previously published studies which show a suppressive effect of Oc on renal function and growth in experimental diabetes. This apparent discrepancy may be related to the duration of treatment or to a biphasic physiological effect of Oc when used in different doses.

Transcriptional profiling of the megabladder mouse: A unique model of bladder dysmorphogenesis

“…Interestingly, exposure of cultured smooth muscle cells to varying concentrations of Urp produced a biphasic response in the expression of SRF. Although the biological basis for this observation remains to be determined, significant precedent exists for small peptide hormones having distinct, dose-dependent biological effects upon their target tissues (Maguire and Davenport, 2005;Wietfeld et al, 2004;Gardiner et al, 2004Rubinger et al, 1998Ray et al, 1993;Ishikawa et al, 1988). Such studies suggest that both ligand and GTP concentration as well as desensitization all play an important role in regulating the ratio of receptor coupling to functionally distinct G-proteins, thereby modulating the precise biological response elicited.…”

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

“…The experimental data regarding diabetic nephropathy are varied. In diabetic rats, glomerular hyperfiltration may worsen or fail to improve with octreotide treatment (37,45). Octreotide administration has also been associated with higher FF, greater proteinuria, and worsened histological lesions in diabetic rats (37).…”