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Effect of octreotide, captopril or insulin on renal changes and UAE in long-term experimental diabetes
H Grønbaek1, I Vogel, R Osterby
1Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark.
Abstract:
Renal and glomerular growth is inherent in early human and experimental diabetes frequently followed by later increase in urinary albumin excretion (UAE). Treatment with angiotensin converting enzyme (ACE) inhibitors has proven effective in delaying progression of human and experimental diabetic renal changes, and so has somatostatin analog treatment in experimental diabetes. The aim of the present study was to investigate three weeks of octreotide and captopril treatment alone or in combination following three months of untreated experimental diabetes, and compare the effects to those of insulin treatment. Diabetes induced significant increases in renal and glomerular growth and urinary albumin excretion. Octreotide and captopril alone and in combination reduced renal but not glomerular size, and the combined administration reduced UAE. None of these schedules affected blood glucose levels. Insulin treatment inducing euglycemia significantly reduced renal and glomerular size and UAE. In conclusion, insulin treatment with normalization of the diabetic metabolic derangement nearly normalizes renal and glomerular growth and UAE after three months of untreated diabetes. The combined treatment of octreotide and captopril was also followed by a significant decrease in renal growth and reduction in UAE compared to placebo treatment without affecting the metabolic control of the diabetic animals.
Insights
Diabetic kidney disease shows increased renal growth and albuminuria. Insulin normalized these changes, while octreotide and captopril reduced renal size and albuminuria without affecting blood glucose.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus is associated with progressive renal and glomerular hypertrophy.
- Diabetic nephropathy often presents with increased urinary albumin excretion (UAE).
- Angiotensin-converting enzyme (ACE) inhibitors and somatostatin analogs show potential in managing experimental diabetic nephropathy.
Purpose of the Study:
- To evaluate the effects of octreotide and captopril, alone or in combination, on established diabetic renal changes.
- To compare these effects with insulin treatment in a model of experimental diabetes.
Main Methods:
- Induction of diabetes in experimental models.
- Administration of octreotide, captopril, their combination, or insulin for three weeks after three months of untreated diabetes.
- Assessment of renal and glomerular size, urinary albumin excretion (UAE), and blood glucose levels.
Main Results:
- Diabetes significantly increased renal and glomerular size and UAE.
- Octreotide and captopril reduced renal size but not glomerular size; combined therapy reduced UAE.
- Insulin treatment normalized renal and glomerular size and UAE by achieving euglycemia.
- Neither octreotide nor captopril affected blood glucose levels.
Conclusions:
- Insulin therapy, by normalizing metabolic derangements, effectively reverses established diabetic renal and glomerular hypertrophy and reduces UAE.
- Combined octreotide and captopril treatment demonstrates efficacy in reducing renal growth and UAE in diabetic animals, independent of glycemic control.