D-chiro-inositol--its functional role in insulin action and its deficit in insulin resistance.
In this review we discuss the biological significance of D-chiro-inositol, originally discovered as a component of a putative mediator of intracellular insulin action, where as a putative mediator, it accelerates the dephosphorylation of glycogen synthase and pyruvate dehydrogenase, rate limiting enzymes of non-oxidative and oxidative glucose disposal. Early studies demonstrated a linear relationship between its decreased urinary excretion and the degree of insulin resistance present. When tissue contents, including muscle, of type 2 diabetic subjects were assayed, they demonstrated a more general body deficiency. Administration of D-chiro-inositol to diabetic rats, Rhesus monkeys and now to humans accelerated glucose disposal and sensitized insulin action. A defect in vivo in the epimerization of myo-inositol to chiro-inositol in insulin sensitive tissues of the GK type 2 diabetic rat has been elucidated. Thus, administered D-chiro-inositol may act to bypass a defective normal epimerization of myo-inositol to D-chiro-inositol associated with insulin resistance and act to at least partially restore insulin sensitivity and glucose disposal.
Larner
Joseph
J
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908, USA. jlarner@insmed.com
D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D006006:Glycogen Synthase / Q000378:metabolism; D007294:Inositol / Q000737:chemistry / Q000172:deficiency* / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008253:Macaca mulatta; D009765:Obesity / Q000503:physiopathology; D051381:Rats; D013237:Stereoisomerism
D001786:Blood Glucose; D007328:Insulin; D007294:Inositol; D006006:Glycogen Synthase