Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol

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Abstract
To assess the potential of myo -inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5,1, or 2% myo -inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo -inositol supplementation, 1 ) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, 2 ) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, 3 ) regional blood flows were measured with 15-μm 85Sr-labeled microspheres, and 4 ) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart, myo -inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo -inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo -inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo -inositol diet, myo -inositol had minimal if any effects on the above parameters in control rats. These observations indicate that diabetes-induced increases in regional blood flow, 131I-BSA permeation, GFR, and urinary protein excretion can be markedly reduced or normalized by consumption of myo -inositol-supplemented diets that raise plasma myo -inositol levels approximately fivefold. The failure of the 2% myo -inositol diet to normalize GFR and blood flow and albumin permeation in several tissues despite markedly elevated plasma myo -inositol levels and normal or elevated tissue myo -inositol levels indicates that if vascular functional changes in these tissues are linked to altered myo -inositol levels, they are resistant to normalization by elevation of plasma myo -inositol levels. These results suggest that other factors independent of changes in relative or absolute tissue myo -inositol levels may play an important role in the pathogenesis of diabetes-induced vascular functional changes in these tissues. The finding that myo -inositol-supplemented diets had no effect on body weight gain, renal hypertrophy, or urine volume indicates that these changes were not linked to imbalances in myo -inositol metabolism.