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Elevated glucose increases mesangial cell sensitivity to insulin-like growth factor I
M J Horney1, D W Shirley, D T Kurtz
1Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
The American Journal of Physiology
|December 5, 1998
Summary
High glucose reduces insulin-like growth factor binding protein 2 (IGFBP-2) in mesangial cells. This enhances IGF-I-induced proliferation, potentially contributing to diabetic glomerulosclerosis.
Area of Science:
- Cell Biology
- Endocrinology
- Nephrology
Background:
- Diabetic nephropathy is a major complication of diabetes.
- Mesangial cell proliferation contributes to glomerulosclerosis.
- Insulin-like growth factor I (IGF-I) plays a role in cell growth and diabetic kidney disease.
Purpose of the Study:
- To investigate the effect of high glucose on IGF-I-induced mesangial cell (MC) proliferation.
- To examine the relationship between IGF binding protein 2 (IGFBP-2) secretion and MC proliferation under high glucose conditions.
Main Methods:
- Murine mesangial cells (MMCs) were cultured in normal (NG) and high glucose (HG) conditions.
- IGFBP-2 secretion, mRNA levels, and IGF-I-stimulated signaling pathways were assessed.
- Cell proliferation was measured using [3H]thymidine incorporation and cell counting.
Main Results:
- High glucose significantly reduced IGFBP-2 secretion and mRNA levels in MMCs.
- IGF-I-stimulated proliferation, measured by [3H]thymidine incorporation and cell number, was enhanced in high glucose.
- High glucose increased IGF-I-stimulated insulin receptor substrate-1/2 phosphorylation and activator protein-1 transcriptional activity.
Conclusions:
- Hyperglycemia may increase mesangial cell sensitivity to IGF-I by downregulating IGFBP-2.
- Reduced IGFBP-2 levels contribute to increased MC proliferation and secretory responses under high glucose.
- These mechanisms may play a role in the pathogenesis of diabetic glomerulosclerosis.