Modulation of Hemodynamic and Vascular Filtration Changes in Diabetic Rats by Dietary myo-inositol
- Giuseppe Pugliese,
- Ronald G Tilton,
- Amanda Speedy,
- Elettra Santarelli,
- Donald M Eades,
- Michael A Province,
- Charles Kilo,
- William R Sherman and
- Joseph R Williamson
- Departments of Pathology, Medicine, and Psychiatry and the Division of Biostatistics, Washington University School of Medicine St. Louis, Missouri
- Address correspondence and reprint requests to Ronald G. Tilton, PhD, Department of Pathology, Box 8118, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110.
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.
- Received April 3, 1989.
- Revision received October 30, 1989.
- Accepted October 30, 1989.
- Copyright © 1990 by the American Diabetes Association