Elevated glucose increases mesangial cell sensitivity to insulin
-like growth factor-1.
Horney, Mark J., David W. Shirley, David T. Kurtz, and Steven A.
Rosenzweig.
Department of Cell and Molecular Pharmacology and Experimental
Therapeutics, Medical University of South Carolina, Charleston, SC
29425
APStracts 5:0047F, 1998.
To determine the effects of glucose on insulin-like growth factor-1
(IGF-1)-induced mesangial cell (MC) proliferation, we have examined
the relationships between IGF binding protein-2 (IGFBP-2) secretion
and proliferation in murine MCs (MMCs). MMCs incubated in high
glucose (HG, 25 mM) exhibited a 25-30% reduction in IGFBP-2 secretion
compared to cells in normal glucose (NG, 5.6 mM). This loss was not
due to cell surface binding; it correlated with a 3.1-fold decrease
in IGFBP-2 mRNA. IGFBP-2 secretion was stimulated by IGF-1 in NG but
was unaltered in HG. Insulin treatment yielded similar results at 10
-fold higher doses, indicating that this response is IGF-1 receptor
-dependent. MMCs in HG displayed increased IGF-1-stimulated insulin
receptor substrate-1/2 phosphorylation and activator protein-1
transcriptional activity compared to NG controls. Accordingly, while
IGF-1 was not proliferative in NG, it increased [3H]-thymidine
incorporation and cell number in HG to an extent proportional to the
decrease in IGFBP-2. Thus, hyperglycemia, as seen in diabetes, may
increase MC IGF-1 sensitivity by reducing IGFBP-2 expression, in turn
increasing their proliferative and secretory responses and
contributing to the development of diabetic glomerulosclerosis.
Received 17 November 1997; accepted in final form 11 February
1998.
APS Manuscript Number F359-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 9 March 1998