chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects.
chiro- and myo-Inositols are major components of the two inositol phosphoglycan mediators of insulin action. Previous work in this laboratory has shown hypo-chiro-inositoluria in type II diabetic subjects and decreased chiro-inositol in mediator prepared from skeletal-muscle biopsies of Pima Indian diabetic subjects together with increased myo-inositol concentrations. Because mediator bioactivity was not previously examined, we decided to isolate the two types of insulin mediator from hemodialysate, urine, and autopsy muscle to investigate their bioactivity in control and type II diabetic subjects. Human mediator fractions were isolated at pH 2.0 and pH 1.3 from hemodialysate, urine, and autopsy muscle of type II diabetic subjects and nondiabetic control subjects. Mediators were assayed for bioactivity, and the relative chiro-inositol/myo-inositol concentration ratio was determined for the mediator pH 2.0 samples by using HPLC or GC/MS. Regardless of source, the chiro-inositol-containing mediator pH 2.0 fractions from type II diabetic subjects were markedly less active than those from controls (50% or less) (P < 0.05). In addition, the chiro-inositol/myo-inositol ratio in samples from type II subjects was significantly reduced (1/3-1/9) compared with controls (P < 0.05 for hemodialysate and P < 0.01 for muscle samples). In contrast, no difference in bioactivity was seen in myo-inositol-containing mediator pH 1.3 samples isolated from the same type II diabetic and control subjects. In type II diabetes there is a generalized deficiency of chiro-inositol mediator in the body in terms of both decreased chiro-inositol mediator (pH 2.0) bioactivity and chiro-inositol content.
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
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Asplin
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Galasko
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Larner
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D015312:Hemodialysis Solutions / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007294:Inositol / Q000032:analysis / Q000172:deficiency*; D007295:Inositol Phosphates / Q000032:analysis* / Q000302:isolation & purification; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000737:chemistry*; D011134:Polysaccharides / Q000032:analysis* / Q000302:isolation & purification; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism
D015312:Hemodialysis Solutions; D007295:Inositol Phosphates; D011134:Polysaccharides; C028039:inositol phosphate glycan; D007294:Inositol; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase