Regional changes in the intrarenal insulin-like growth factor-I axis in diabetes

Fernando Custodio Fervenza, Tanny Tsao, Andrew R. Hoffman, Ralph Rabkin

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Since insulin-like growth factor-I (IGF-I) has been shown to promote renal growth and as kidney IGF-I content increases during the early days after the onset of diabetes, it is likely that this growth factor contributes to initial diabetic renal hypertrophy. However, it is unclear whether IGF-I contributes to the continued renal growth that occurs in diabetes. Since IGF-I action is mediated through its receptor and as its bioavailability is regulated by IGF binding proteins (IGFBP), we postulated that changes in IGF-I receptor binding or IGFBP production may favor a role for IGF-I in diabetic renal growth when kidney IGF-I levels have returned to normal. To test this thesis, we studied kidneys of rats after seven days of streptozotocin diabetes. In diabetic cortex and medulla, growth hormone receptor mRNA levels and IGF-I and IGF-I receptor mRNA and protein product levels were unchanged. In cortex IGFBP-1 mRNA levels were increased while IGFBP-2 and -4 mRNA levels decreased. In medulla the only change was a fall in IGFBP-1 mRNA levels. Using Western ligand blot we observed an increase in a 32 kDa plasma membrane-associated IGFBP. Insulin therapy reversed all changes except the elevated cortical IGFBF-1 mRNA levels, indicating the presence of regional heterogeneity in the IGFBP response to diabetes in the kidney. However, the lack of change in IGF-I, IGF-I receptor and growth hormone receptor gene expression and protein products after one week of diabetes argues against a role for IGF-I in sustaining diabetic renal growth beyond the initial growth phase.

Original languageEnglish (US)
Pages (from-to)811-818
Number of pages8
JournalKidney International
Volume51
Issue number3
StatePublished - 1997
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor I
Kidney
Insulin-Like Growth Factor Binding Proteins
IGF Type 1 Receptor
Messenger RNA
Somatotropin Receptors
Insulin-Like Growth Factor Binding Protein 1
Growth
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 2
Experimental Diabetes Mellitus
Hypertrophy
Biological Availability
Intercellular Signaling Peptides and Proteins
Membrane Proteins
Proteins
Western Blotting
Cell Membrane
Insulin
Ligands

ASJC Scopus subject areas

  • Nephrology

Cite this

Regional changes in the intrarenal insulin-like growth factor-I axis in diabetes. / Fervenza, Fernando Custodio; Tsao, Tanny; Hoffman, Andrew R.; Rabkin, Ralph.

In: Kidney International, Vol. 51, No. 3, 1997, p. 811-818.

Research output: Contribution to journalArticle

Fervenza, FC, Tsao, T, Hoffman, AR & Rabkin, R 1997, 'Regional changes in the intrarenal insulin-like growth factor-I axis in diabetes', Kidney International, vol. 51, no. 3, pp. 811-818.
Fervenza, Fernando Custodio ; Tsao, Tanny ; Hoffman, Andrew R. ; Rabkin, Ralph. / Regional changes in the intrarenal insulin-like growth factor-I axis in diabetes. In: Kidney International. 1997 ; Vol. 51, No. 3. pp. 811-818.
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