IN-VIVO CHIRO-INOSITOL METABOLISM IN THE RAT - A DEFECT IN CHIRO-INOSITOL SYNTHESIS FROM MYOINOSITOL AND AN INCREASED INCORPORATION OF CHIRO-[H-3]INOSITOL INTO PHOSPHOLIPID IN THE GOTO-KAKIZAKI (GK) RAT

We report our comparative studies of myo- and chiro[H-3]inositol distr ibution in control nondiabetic Wistar and spontaneous nonobese insulin -resistant Type II diabetic G,K, rat tissues following 78-h labeling p eriod. From various tissue extracts, free inositols, inositol phosphat es, and inositol phospholipids were isolated and analyzed. Our finding s demonstrate (1) a significant difference in the metabolism of myo- a nd chiro-inositol in normal Wistar and G,K, rats, (2) a severe defect in conversion of myo-[H-3]inositol to chiro[H-3]inositol at the inosit ol phospholipid level of insulin-sensitive tissues of the G,K, rat, (3 ) an increased incorporation of myo-[H-3]inositol into purified inosit ol phospholipids of the G,K, rat consistent with a decreased conversio n to chiro-[H-3]inositol, (4) the presumed presence of a pathway which incorporates chiro-[H-3]inositol into inositol phospholipids, and whi ch is overactive in the G,K, rat compared to the Wistar rat, and (5) n o or minimal conversion of chiro[H-3]inositol to myo-[H-3]inositol.