Diabetes, Vol 39, Issue 3 312-322, Copyright © 1990 by American Diabetes Association

ARTICLES

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

G Pugliese, RG Tilton, A Speedy, E Santarelli, DM Eades, MA Province, C Kilo, WR Sherman and JR Williamson
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 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-microns 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.(ABSTRACT TRUNCATED AT 400 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Q. Xu, T. Qaum, and A. P. Adamis Sensitive Blood-Retinal Barrier Breakdown Quantitation Using Evans Blue Invest. Ophthalmol. Vis. Sci., March 1, 2001; 42(3): 789 - 794. [Abstract] [Full Text]

				N. K. Worrall, K. Chang, G. M. Suau, W. S. Allison, T. P. Misko, P. M. Sullivan, R. G. Tilton, J. R. Williamson, and T. B. Ferguson Jr Inhibition of Inducible Nitric Oxide Synthase Prevents Myocardial and Systemic Vascular Barrier Dysfunction During Early Cardiac Allograft Rejection Circ. Res., May 1, 1996; 78(5): 769 - 779. [Abstract] [Full Text]