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ORIGINAL RESEARCH ARTICLE

Kidney Growth in Normal and Diabetic Mice Is Not Affected by Human Insulin-Like Growth Factor Binding Protein-1 Administration

Vesna Cingel-Risti^*,1, Bieke F. Schrijvers, Arlène K. van Vliet^*, Ruth Rasch, Victor K. M. Han, Stenvert L. S. Drop^* and Allan Flyvbjerg

^* Laboratory of Pediatrics, Subdivision of Molecular Endocrinology, Erasmus MC, Rotterdam, The Netherlands; Medical Research Laboratories, Clinical Institute, Aarhus University Hospital, Aarhus, Denmark; Department of Cell Biology, Institute of Anatomy and Electron Microscopy and Stereological Research Laboratory, Aarhus University, Aarhus, Denmark; and CIHR Group in Fetal and Neonatal Health and Development, Lawson Research Institute, University of Western Ontario, London, Ontario, Canada

To whom requests for reprints should be addressed at ¹ Laboratory of Pediatrics, Room Ee1500, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: v.cingel{at}erasmusmc.nl

Insulin-like growth factor I (IGF-I) accumulates in the kidney following the onset of diabetes, initiating diabetic renal hypertrophy. Increased renal IGF-I protein content, which is not reflected in messenger RNA (mRNA) levels, suggests that renal IGF-I accumulation is due to sequestration of circulating IGF-I rather than to local synthesis. It has been suggested that IGF-I is trapped in the kidney by IGF binding protein 1 (IGFBP-1). We administered purified human IGFBP-1 (hIGFBP-1) to nondiabetic and diabetic mice as three daily sc injections for 14 days, starting 6 days after induction of streptozotocin diabetes when the animals were overtly diabetic. Markers of early diabetic renal changes (i.e., increased kidney weight, glomerular volume, and albuminuria) coincided with accumulation of renal cortical IGF-I despite decreased mRNA levels in 20-day diabetic mice. Human IGFBP-1 administration had no effect on increased kidney weight or albuminuria in early diabetes, although it abolished renal cortical IGF-I accumulation and glomerular hypertrophy in diabetic mice. Increased IGF-I levels in kidneys of normal mice receiving hIGFBP-1 were not reflected on kidney parameters. IGFBP-1 administration in diabetic mice had only minor effects on diabetic renal changes. Accordingly, these results did not support the hypothesis that IGFBP-1 plays a major role in early renal changes in diabetes.

Key Words: diabetes • growth hormone • insulin-like growth factor I • insulin-like growth factor binding protein 1 • mouse