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Effect of octreotide on experimental diabetic renal and glomerular growth: importance of early intervention
H Grønbaek1, B Nielsen, J Frystyk
1Institute of Experimental Clinical Research, Aarhus Kommunehospital, Denmark.
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.
Insights
Early intervention with octreotide in diabetic rats prevents kidney growth by inhibiting insulin-like growth factor-I (IGF-I) accumulation. Delayed treatment is less effective, showing early IGF-I is crucial for diabetic kidney hypertrophy.
Area of Science:
- Nephrology
- Endocrinology
- Diabetology
Background:
- Insulin-like growth factor-I (IGF-I) is a key renotropic factor in early diabetes.
- Streptozotocin-induced diabetes in rats causes significant renal hypertrophy.
Purpose of the Study:
- To investigate the efficacy of somatostatin analogue (octreotide) treatment initiated at different time points in preventing diabetic kidney growth.
- To determine the role of early IGF-I accumulation in diabetic nephropathy.
Main Methods:
- Rats were induced with diabetes using streptozotocin.
- Octreotide treatment was administered at varying intervals after diabetes onset (days 0, 3, 5, 7, 9).
- Renal growth, protein and DNA accumulation, glomerular volume, and IGF-I levels were assessed.
Main Results:
- Early octreotide intervention (initiated at diabetes onset) significantly reduced renal growth compared to placebo.
- Delayed octreotide treatment showed diminishing efficacy in reducing renal growth.
- Octreotide reduced kidney and serum IGF-I levels, particularly with early intervention.
- No significant changes were observed in protein accumulation, DNA increase, or glomerular volume.
Conclusions:
- Early accumulation of renal IGF-I is essential for the development of diabetic kidney hypertrophy in rats.
- Octreotide treatment is most effective when initiated early, preventing IGF-I accumulation and subsequent renal growth.
- Delayed octreotide administration cannot reverse established renal and glomerular hypertrophy in this diabetic model.