Diabetes and the myo-inositol paradox.

Abstract:

:To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical techniques in layers of the cornea, the aortic myointima, the cardiac left ventricle and atrioventricular node (AVN), and retina and kidney after 19 days or 2 mo (mildly diabetic non-insulin-treated [MD] and severely diabetic insulin-treated [SD] groups) in the alloxan-induced diabetes model. In the aqueous humor, glucose rose linearly with increased serum glucose, sorbitol was markedly increased in the MD and SD groups, and myo-inositol did not change in any diabetic group. There was no change in glucose or sorbitol in aortic myointima in any group, but myoinositol was decreased in 19-day diabetic rabbits by 26%, unchanged in MD rabbits but paradoxically increased by 60% in SD rabbits. Glucose, sorbitol, and myo-inositol increased in all three corneal layers in SD rabbits but only in epithelium and stroma in 19-day and MD rabbits. AVN glucose and sorbitol did not change in 19-day diabetic, MD, or SD diabetic rabbits. AVN myo-inositol was three times higher than ventricular myo-inositol and did not appear to change in SD rabbits. Retinal pigmented epithelium myo-inositol was decreased 30% in SD rabbits. Glomerular myo-inositol was also decreased, but not significantly, in SD rabbits. We conclude that the paradoxical increase in corneal and aortal myo-inositol raises fundamental questions about the general applicability of the myo-inositol-depletion hypothesis.

journal_name

Diabetes

journal_title

Diabetes

authors

Loy A,Lurie KG,Ghosh A,Wilson JM,MacGregor LC,Matschinsky FM

doi

10.2337/diab.39.10.1305

subject

Has Abstract

pub_date

1990-10-01 00:00:00

pages

1305-12

issue

10

eissn

0012-1797

issn

1939-327X

journal_volume

39

pub_type

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