Effect of octreotide on experimental diabetic renal and glomerular growth: importance of early intervention

Abstract

IGF-I acts as a renotropic factor in early streptozotocin-induced diabetes. Somatostatin analogue (octreotide) treatment initiated at the onset of diabetes prevents kidney IGF-I accumulation and renal growth. Seven days of octreotide treatment initiated after 3, 5, 7 or 9 days of untreated diabetes was investigated. Diabetic renal hypertrophy was followed by renal hyperplasia. Compared with placebo-treated diabetic rats, the earliest octreotide intervention was followed by a greater reduction in renal growth compared with intervention later on (days 3 to 10, 12%; days 5 to 12, 10%; days 7 to 14, 9%; days 9 to 16, 6%; P < 0.05). Octreotide treatment was unable to reduce protein accumulation and kidney DNA increase consistently. No difference in glomerular volume fraction or total glomerular volume was observed between placebo- and octreotide-treated diabetic rats. Octreotide treatment was followed by reduced kidney and serum IGF-I especially following early intervention, while no effect over that of diabetes was observed in the later intervention periods. The results confirm the notion that initial renal IGF-I accumulation is a prerequisite for early diabetic kidney hypertrophy in rats and show that delayed octreotide treatment cannot reverse renal and glomerular growth which is already manifest.

Inhibitory effects of octreotide on renal and glomerular growth in early experimental diabetes in mice

“…In the diabetic rat models, only a transient early increase in kidney IGF-I levels is observed (Flyvbjerg et al 1989, Grønbaek et al 1996. Further, the kidney IGF-I increase seems to be important as postponement of octreotide treatment to 3-9 days after the induction of diabetes is followed by less significant inhibition of renal and glomerular growth (Grønbaek et al 1995b). In the present study, octreotide treatment significantly reduced kidney IGF-I levels after 7 days, but not by the end of the study, and elevated IGF-I levels were observed in both diabetic groups compared with controls by day 14.…”