Expression of insulin-like growth factor binding proteins in the rat kidney: Effects of long-term diabetes

Daniel Landau, Edward Chin, Carolyn Bondy, Horacio Domene, Charles T. Roberts, Henning Gronbaek, Allan Flyvbjerg, Derek Le Roith

Research output: Contribution to journalArticle

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Abstract

Recent studies have shown that the renal synthesis of insulin-like growth factor binding proteins (IGFBPs) is altered in insulin-deficient diabetes mellitus, suggesting that these changesmay be implicated in the alterations in renal function and morphology that accompany diabetes. To investigate the time course and the precise cellular distribution of changes in IGFBP expression, we used quantitative in situ hybridization to analyze renal IGF-I and IGFBP-1 to -5 messenger RNA (mRNA) localization and levels from 2 days to 6 months after the onset of streptozotocin-induced diabetes. There was an immediate sharp decline in IGF-I mRNA levels in the outer medulla that persisted for up to 3 months and a much smaller reduction in IGF-I mRNA levels in the medullary thick ascending limbs (MTALs). In nondiabetic animals, IGFBP-1 mRNA is most abundant in the MTALs. Immediately after the induction of diabetes, however, there was a greater than 2-fold increase in cortical IGFBP-1 mRNA and a 75% decrease in IGFBP-1 mRNA in MTALs. These changes persisted for up to 6 months in the diabetic animals. In contrast, IGFBP-5 mRNA levels were increased in the outer medulla and decreased in the cortex of diabetic kidneys. No significant changes in renal IG-FBP-2 mRNA levels or distribution were noted, and changes in IG-FBP-3 and -4 mRNA levels were subtle. In summary, streptozotocin-induced diabetes is associated with very prominent and complex alterations in renal IGF system gene expression, including robust increases in cortical IGFBP-1 and profound decreases in cortical IG-FBP-5 mRNA and medullary IGF-I mRNA levels. The divergent changes in IGFBP-1 and -5 mRNA levels in cortex vs. outer medulla indicate that regulation of IGFBP mRNA levels is quite complex.

Original languageEnglish (US)
Pages (from-to)1835-1842
Number of pages8
JournalEndocrinology
Volume136
Issue number5
DOIs
StatePublished - May 1995
Externally publishedYes

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Insulin-Like Growth Factor Binding Proteins
Kidney
Messenger RNA
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor I
Insulin-Like Growth Factor Binding Protein 5
Experimental Diabetes Mellitus
Extremities
Kidney Cortex
In Situ Hybridization
Diabetes Mellitus

ASJC Scopus subject areas

  • Endocrinology

Cite this

Expression of insulin-like growth factor binding proteins in the rat kidney : Effects of long-term diabetes. / Landau, Daniel; Chin, Edward; Bondy, Carolyn; Domene, Horacio; Roberts, Charles T.; Gronbaek, Henning; Flyvbjerg, Allan; Le Roith, Derek.

In: Endocrinology, Vol. 136, No. 5, 05.1995, p. 1835-1842.

Research output: Contribution to journalArticle

Landau, D, Chin, E, Bondy, C, Domene, H, Roberts, CT, Gronbaek, H, Flyvbjerg, A & Le Roith, D 1995, 'Expression of insulin-like growth factor binding proteins in the rat kidney: Effects of long-term diabetes', Endocrinology, vol. 136, no. 5, pp. 1835-1842. https://doi.org/10.1210/endo.136.5.7536658
Landau, Daniel ; Chin, Edward ; Bondy, Carolyn ; Domene, Horacio ; Roberts, Charles T. ; Gronbaek, Henning ; Flyvbjerg, Allan ; Le Roith, Derek. / Expression of insulin-like growth factor binding proteins in the rat kidney : Effects of long-term diabetes. In: Endocrinology. 1995 ; Vol. 136, No. 5. pp. 1835-1842.
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