The IGF-I axis has been implicated in the development of renal complications of diabetes. Glomerulosclerosis of diabetes is characterized by mesangial cell proliferation and accumulation of extracellular matrix in the mesangium. This suggests that there may be an intrinsic defect of mesangial cell behavior. Non-obese diabetic mice (NOD) develop glomerular lesions early after the onset of IDDM. We developed new lines of mesangial cells derived from these animals to study the role of the IGF-I axis in a model of spontaneous diabetes. We examined the IGF-I receptor, IGF-I production, and IGF-I binding proteins of the NOD mice and compared them to control mesangial cells. We previously demonstrated the presence of IGF-I receptors and the synthesis of IGF-I in glomerular mesangial cells. In the current study we examined mouse glomerular endothelial and epithelial cells in culture for IGF-I receptors. [125I]IGF-I specifically bound to the cell surface of both cell types. Maximum specific binding, 0.141 B/F for endothelial cells and 0.301 B/F for epithelial cells, was obtained at 22 C after 150 min incubation. The estimated Kd values were 2.25x10 for endothelial cells and 1.5x10 for epithelial cells. Cross- linking studies showed a single band of radioactivity with an estimated mol. wt. of 145kD, consistent with the alpha-subunit of the IGF-I receptor. Radiolabelled IGF-I was not degraded by either cell types. These findings suggested a paracrine role of IGF-I in the glomerulus.
