Chronic exposure to high glucose decreases myo-inositol in cultured cerebral microvascular pericytes but not in endothelium.
It has been proposed that the development of diabetic complications may involve a depletion of cellular myo-inositol due to an increase in polyol (sorbitol) formation. We therefore initially examined the effect of diabetes on levels of these metabolites in isolated cerebral microvessels. Compared with microvessels from control rats, microvessels from diabetic animals showed no detectable alteration in myo-inositol levels and a small increase in sorbitol content. To assess whether myo-inositol depletion might occur in only certain microvascular cells, cultured bovine cerebral microvascular pericytes and endothelium were grown for 3 or 18-20 days at 1.1, 5.5, or 22.2 mmol/l glucose. Increased medium glucose concentration resulted in increased sorbitol content in both cell types after both periods of incubation (p less than 0.05). In contrast, a significant decrease in myo-inositol content (22%, p less than 0.01) was observed only in pericytes grown for 18-20 days in the high glucose medium. Neither the adenosine 5'-triphosphate content nor the adenosine 5'-triphosphate/adenosine 5'-diphosphate (ATP/ADP) ratio of the pericytes was affected by the medium glucose concentration, indicating that the decrease in myo-inositol was not caused by a deficiency in the cellular energy state affecting the active transport of myo-inositol. These data suggest that myo-inositol depletion occurs selectively in the pericyte, a cell type known to be the site of early morphological changes in diabetes. Furthermore, the depletion apparently requires prolonged exposure to high glucose and is not due to a change in energy state.
Sussman
I
I
Evans Memorial Department of Medicine, Boston University School of Medicine, Massachusetts.
Carson
M P
MP
Schultz
V
V
Wu
X P
XP
McCall
A L
AL
Ruderman
N B
NB
Tornheim
K
K
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013012:Sorbitol / Q000378:metabolism
D007294:Inositol; D013012:Sorbitol; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose