Phosphoinositol glycan derived mediators and insulin resistance. Prospects for diagnosis and therapy.

While much work remains, the evidence has become strong that IPG generation following insulin action is a significant signaling mechanism. A considerable body of data has established IPG release by insulin and other growth factors from cell membranes, cells and in human blood and muscle biopsies in vivo. Two separate IPG species containing D-chiro-inositol and myo-inositol have been separated by ion exchange. These IPGs have separate actions in vitro and are both active as insulin surrogates in vivo. A deficiency of the chiro-inositol system has been demonstrated in urine and tissues in humans and directly related to insulin resistance. Accordingly, D-chiro-inositol was administered to STZ diabetic rats and rhesus monkeys and shown to decrease hyperglycemia and enhance glucose disposal. Two trials in humans with impaired glucose tolerance and women with PCOS have now also proven successful. Thus, the pathophysiology in the chiro-inositol system related to insulin resistance and its reversal by chiro-inositol administration, in addition to the basic work, argues strongly for the physiological significance of this novel signaling system in the control of glucose metabolism.