Lipids and cellular Na+/H+ antiport activity in diabetic nephropathy

Increased cellular Na+/H+ antiport activity has been documented in various cell types from hypertensive humans and rats. This membrane abnormality may be associated with the thickening of the vascular media of resistance vessels. Such an abnormality has also been demonstrated in cells from type I diabetic patients with nephropathy, and may indicate the predisposition to essential hypertension in such patients. We now demonstrate the importance of the rate-limiting enzyme for cholesterol and isoprenoid synthesis, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, in determining cellular Na+/H+ antiport activity. This finding may have application in the future treatment of diabetic patients with proteinuria.