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Effects of the somatostatin analogue octreotide on renal function in conscious diabetic rats
M Bak1, K Thomsen, A Flyvbjerg
1Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Aarhus University Hospital, Skovagervej, Risskov, Denmark. martinbak@dadlnet.dk
Background:
Studies performed during the last decade have indicated that growth hormone (GH) and insulin-like growth factors (IGFs) may mediate the early renal changes in diabetes mellitus, i.e. hypertrophy and hyperfiltration. This and other observations have led to the suggestion that GH/IGF inhibitors, such as long-acting somatostatin analogue (e.g. octreotide and lanreotide), may be useful in order to inhibit or prevent development of long-term diabetic complications.
Methods:
The present study examined the acute and chronic effects of octreotide on renal function following induction of streptozotocin (STZ)-diabetes in rats. The studies were carried out in conscious, non-fasted diabetic animals.
Results:
Chronic administration of octreotide for 7 days, from onset of diabetes, prevented the decrease of effective renal vascular resistance (ERVR), and the increases in filtration fraction (FF), glomerular filtration rate (GFR), and absolute proximal tubular fluid reabsorption (APR) induced by diabetes. The renal hypertrophy was only partially prevented. In the acute study, similar changes were observed in effective renal plasma flow (ERPF) and ERVR but FF increased and GFR remained unaltered.
Conclusions:
Chronic but not acute treatment with octreotide prevented the renal hyperfiltration caused by diabetes. This effect is most likely due to an increase in afferent arteriolar resistance.
Insights
Chronic octreotide treatment prevents diabetes-induced renal hyperfiltration in rats by increasing afferent arteriolar resistance. This suggests potential for growth hormone/insulin-like growth factor inhibitors in managing diabetic kidney complications.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Growth hormone (GH) and insulin-like growth factors (IGFs) are implicated in early diabetic nephropathy, causing renal hypertrophy and hyperfiltration.
- GH/IGF inhibitors, like somatostatin analogues (octreotide, lanreotide), are proposed to prevent long-term diabetic kidney complications.
Purpose of the Study:
- To investigate the acute and chronic effects of octreotide on renal function in streptozotocin-induced diabetic rats.
Main Methods:
- Conscious, non-fasted diabetic rats were administered octreotide.
- Renal function parameters including effective renal plasma flow (ERPF), effective renal vascular resistance (ERVR), filtration fraction (FF), glomerular filtration rate (GFR), and absolute proximal tubular fluid reabsorption (APR) were measured.
Main Results:
- Chronic octreotide (7 days) prevented diabetes-induced increases in FF, GFR, and APR, and normalized ERVR. Renal hypertrophy was partially inhibited.
- Acute octreotide administration showed similar effects on ERPF and ERVR, but GFR remained unchanged and FF increased.
Conclusions:
- Chronic octreotide administration effectively prevented diabetes-related renal hyperfiltration in rats.
- The protective effect is likely mediated by increased afferent arteriolar resistance.