Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats

• Published in: Diabetes (New York, N.Y.) Vol. 47; no. 6; pp. 924 - 930
• Main Authors: RAZ, I, RUBINGER, D, POPOVTZER, M, GRØNBAEK, H, WEISS, O, FLYVBJERG, A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-06-1998
• Subjects: Animals; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - drug effects; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - physiopathology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; General and cellular metabolism. Vitamins; Growth Hormone - blood; Insulin - blood; Insulin-like growth factor 1; Insulin-Like Growth Factor Binding Protein 1 - biosynthesis; Insulin-like growth factor I; Insulin-Like Growth Factor I - biosynthesis; Kidney; Kidney - drug effects; Kidney - metabolism; Kidneys; Kinetics; Male; Medical sciences; Octreotide - blood; Octreotide - pharmacology; Organ Size - drug effects; Pharmacology. Drug treatments; Physiological aspects; Rats; Rats, Inbred Strains; Reference Values; RNA, Messenger - biosynthesis; Time Factors; Transcription, Genetic - drug effects; Endocrinopathy; Kidney disease; Urinary system disease; Rat; Diabetes mellitus; Rodentia; Octreotide; Gene expression; Kidney; Insulin like growth factor binding protein; Prevention; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Nephropathy; Treatment; Urinary system; Animal; Complication
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.47.6.924

Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.
I Raz ,
D Rubinger ,
M Popovtzer ,
H Grønbaek ,
O Weiss and
A Flyvbjerg
Department of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel.
Abstract
The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like
growth factor (IGF)-I concentration. Administration of the long-acting somatostatin analog octreotide to STZ diabetic rats
inhibits the early increase in kidney IGF-I and the increase in kidney size without affecting metabolic control. We studied
the effects of octreotide treatment on the intrarenal IGF axis at 2 and at 7 days after the induction of STZ diabetes. Two
days after induction of diabetes, kidney IGF-I was increased from 850 +/- 43 ng/g tissue in controls to 1,648 +/- 165 ng/g
tissue (P < 0.001) in diabetic animals. The diabetes-associated increase in renal IGF-I 48 h after STZ injection was totally
prevented by octreotide (IGF = 780 +/- 57 ng/g tissue). However, 7 days after the induction of diabetes, kidney IGF-I was
similar to that of control and was not affected by octreotide. No difference in serum IGF-I was observed between controls
and diabetic rats after 2 days of diabetes; however, octreotide treatment resulted in a significant decrease of serum IGF-I
after 2 days when compared with control rats (P < 0.05). Renal IGF-I mRNA was significantly decreased to the same extent in
both diabetic groups 2 and 7 days after the induction of diabetes, while renal IGF-I receptor (IGF-IR) mRNA was unchanged
in rats from either group. Two days after induction of diabetes, renal insulin-like growth factor binding protein (IGFBP)-1
mRNA and 30-kDa IGFBPs (containing IGFBP-1) increased by 186 and 192%, respectively, in untreated diabetic animals compared
with controls. Octreotide treatment prevented the diabetes-associated rise in renal IGFBP-1 mRNA and protein. However, 7 days
after the induction of diabetes, renal IGFBP-1 mRNA and protein were similarly increased in both octreotide-treated or untreated
diabetic rats. Renal IGFBP-3 gene expression and protein and IGFPB-5 mRNA remained unchanged after 2 and 7 days of diabetes
when treated or untreated with octreotide. We conclude that the well-known inhibitory effect of octreotide on the early increase
in renal IGF-I concentration and renal size in diabetes may be mediated through a direct effect on renal IGFBP-1 levels.