Octreotide prevents the early increase in renal insulin-like growth factor binding protein 1 in streptozotocin diabetic rats.
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.
Raz
I
I
Department of Internal Medicine, Hadassah University Hospital, Jerusalem, Israel.
Rubinger
D
D
Popovtzer
M
M
Grønbaek
H
H
Weiss
O
O
Flyvbjerg
A
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D013006:Growth Hormone / Q000097:blood; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D015282:Octreotide / Q000097:blood / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide