CHIRO-INOSITOL DEFICIENCY AND INSULIN-RESISTANCE - A COMPARISON OF THE CHIRO-INOSITOL-CONTAINING 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 phos phoglycan mediators of insulin action. Previous work in this laborator y has shown hypo-chiro-inositoluria in type II diabetic subjects and d ecreased chiro-inositol in mediator prepared from skeletal-muscle biop sies of Pima Indian diabetic subjects together with increased myo-inos itol concentrations. Because mediator bioactivity was not previously e xamined, we decided to isolate the two types of insulin mediator from hemodialysate, urine, and autopsy muscle to investigate their bioactiv ity in control and type II diabetic subjects. Human mediator fractions were isolated at pH 2.0 and pH 1.3 from hemodialysate, urine, and aut opsy muscle of type II diabetic subjects and nondiabetic control. subj ects. Mediators were assayed for bioactivity, and the relative chiro-i nositol/myo-inositol concentration ratio was determined for the mediat or pH 2.0 samples by using HPLC or GC/MS. Regardless of source, the ch iro-inositol-containing mediator pH 2.0 fractions from type II diabeti c subjects were markedly less active than those from controls (50% or less) (P < 0.05). In addition, the chiro-inositol/myo-inositol ratio i n samples from type II subjects was significantly reduced (1/3-1/9) co mpared with controls (P < 0.05 for hemodialysate and P < 0.01 for musc le samples). In contrast, no difference in bioactivity was seen in myo -inositol-containing mediator pH 1.3 samples isolated from the same ty pe II diabetic and control subjects. In type II diabetes there is a ge neralized deficiency of chiro-inositol mediator in the body in terms o f both decreased chiro-inositol mediator (pH 2.0) bioactivity and chir o-inositol content.