INSULIN INDUCES RAPID AND SPECIFIC REARRANGEMENT OF THE CYTOSKELETON OF RAT MESANGIAL CELLS IN-VITRO

Mesangial cells (MCs) grown without supplemental insulin (SI(-)MCs) ex press a quiescent phenotype and extracellular matrix (ECM) composition similar to MCs in vivo. In contrast, MCs routinely propagated in insu lin (SI(+)MCs) are stimulated to proliferate, change their phenotype, and produce large amounts of collagens I and III. These effects of ins ulin may in part be mediated through cytoskeletal rearrangement, Diffe rences in cytoskeletal arrangement were compared between SI(-)MCs and SI(+)MCs and 1 hr after addition of insulin (1 nM) or IGF-1 (100 nM) t o SI(-)MCs. Cells were examined by light microscopy, electron microsco py, and immunostaining for specific cytoskeletal proteins and fibronec tin. Insulin induced rapid rearrangement of stress fibers. Surface ruf fling, actin aggregation, vimentin retraction, rearrangement of vincul in in focal adhesions, and fibronectin extraction were apparent. These direct effects of insulin on the SI-MC cytoskeleton occurred before i nsulin-induced changes in ECM composition. IGF-I induced cytoskeletal reorganization distinct from insulin. These observations demonstrate t hat insulin and IGF-I have unique effects on the MC cytoskeleton, whic h in turn may mediate secondary ligand effects on MCs.