SUMMARY

The accumulation of polyols has been previously found in renal glomeruli isolated from streptozocin-in-duced diabetic (STZ-D) rats, although the intraglomeru-lar polyol pathway has not been exactly localized. Because we have previously observed mesangial cell dysfunction in STZ-D rats, we examined whether the polyol pathway exists in mesangial cells as a possible candidate of the cause of cellular dysfunction. The ac-tivities of two polyol pathway enzymes, aldose reduc-tase and sorbitol dehydrogenase, were clearly detected in the crude homogenate of cultured mesangial cells at higher levels than those of whole glomeruli when DL-glyceraldehyde or D-fructose was used as substrate. When cells were incubated in medium containing 55 mM glucose or galactose, a large amount of sorbitol or galactitol was accumulated intracellularly. The accu-mulation of polyols was effectively blocked by an al-dose reductase inhibitor, ICI 128436. These results suggest that the polyol pathway exists in mesangial cells of rat glomeruli and may play a role in the devel-opment of mesangial cell dysfunction found in STZ-D rats. Diabetes 36:240-43, 1987 There has been increasing evidence that the en-hanced activity of polyol pathway plays an impor-tant role in the development of various diabeticcomplications such as cataract, neuropathy, and retinopathy (1,2). Furthermore, recent reports by Cohen et al. (3-5) indicate that diabetic nephropathy might also be caused by sorbitol accumulation in glomeruli. Because the activity of aldose reductase, a key enzyme for sorbitol syn-thesis, was found immunohistochemically in glomerular ep-ithelium (6), sorbitol accumulation in epithelial cells may b