MESANGIAL CELLS FROM DIABETIC NOD MICE CONSTITUTIVELY SECRETE INCREASED AMOUNTS OF INSULIN-LIKE GROWTH FACTOR-I

Experimental evidence has suggested that insulin-like growth factor-I (IGF-I) may contribute to diabetic complications. Previously, we and o thers have shown that normal glomerular mesangial cells have receptors for, synthesize, and exhibit a mitogenic response to IGF-I. We invest igated the IGF-I response in cells derived from a genetic model of dia betes, the nonobese diabetic (NOD) mouse. Mesangial cell lines were de rived from diabetic (D-NOD) and nondiabetic adult mice. D-NOD cells re leased more IGF-I into the supernatant and had a decreased binding of IGF-I to surface receptors. Analysis according to Scatchard revealed a decreased number of receptor sites on D-NOD cells, although the struc ture of the IGF-I receptor visualized by crosslinking was identical fo r both cell types. Preincubation of D-NOD cells with an antibody to IG F-I resulted in an increase in the number of receptor sites. This sugg ested that autocrine IGF-I was responsible for the decrease in D-NOD r eceptor number and that diabetes had resulted in a stable phenotypic c hange.