Insulin-like growth factor binding protein-5 (IGFBP-5) mediates mesangial cell migration through activation of cdc42, and laminin421 binding to integrin 61 (Berfield et al, Am J Physiol Cell Physiol, 29:C589, 2006). Because glomerular expression of laminin 2 is reduced in diabetic rats (Abrass et al, Am J Pathol, 151:1131, 1997), we directly examined the effect of hyperglycemia on mesangial cell migration and laminin 2 expression. Migration mediated by IGFBP-5 is impaired in the presence of 25mM glucose. This reduction in migration was found to result from a loss in mesangial cell synthesis of laminin421, and IGFBP-5-induced migration could be restored by replacing laminin421. Additional studies showed that there was selective reduction in mRNA translation of laminin 2 in the presence of high glucose. Preserved synthesis of laminin 1 indicates that not all proteins are reduced by high glucose and confirms prior data showing that laminin411 cannot substitute for laminin421 in IGFBP-5-mediated migration. Given the importance of mesangial migration in the reparative response to diabetes-associated mesangiolysis, these findings provide new insights into abnormalities associated with diabetic nephropathy and the potential importance of differential control of protein translation in determination of alterations of protein expression.