Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol.
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)
Pugliese
G
G
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Tilton
R G
RG
Speedy
A
A
Santarelli
E
E
Eades
D M
DM
Province
M A
MA
Kilo
C
C
Sherman
W R
WR
Williamson
J R
JR
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D007294:Inositol / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013012:Sorbitol / Q000097:blood
D007457:Iodine Radioisotopes; D012710:Serum Albumin, Bovine; D007294:Inositol; D013012:Sorbitol