Isolation and Partial Characterisation of Insulin-Mimetic Inositol Phosphoglycans from Human Liver

Inositols prevent and reverse endothelial dysfunction in diabetic rat and rabbit vasculature metabolically and by scavenging superoxide

“…D-chiro-inositol ͉ diabetes ͉ NO ͉ insulin ͉ mimetic I nositol phosphoglycans (IPGs) are potentially important putative intracellular mediators of insulin action (1,2). Separate classes have been identified (3), one containing D-chiro-inositol (DCI) and galactosamine (4) and a second containing myo-inositol (myo-INS) and glucosamine (1)(2)(3)(4)(5).…”

“…Separate classes have been identified (3), one containing D-chiro-inositol (DCI) and galactosamine (4) and a second containing myo-inositol (myo-INS) and glucosamine (1)(2)(3)(4)(5). Generated rapidly from lipid and͞or protein precursors in response to insulin, they have insulin-like effects in vitro and in vivo (1,2,4,6,7). Myo-INS phospho-glycans have been prepared by enzymatic cleavage of protein precursors and chemically synthesized (7)(8)(9).…”

Reciprocal Control of Pyruvate Dehydrogenase Kinase and Phosphatase by Inositol Phosphoglycans: Dynamic State Set by “Push-Pull” System

“…Preparation of IPGs-IPG-P and IPG-A extracted from 5 to 10 g of tissue were separated by elution from Amberlite columns (formate form) with HCl, pH 2.0 and pH 1.3, respectively, as described by Nestler et al (30) and as modified by Caro et al (16). The freeze-dried fractions were stored at Ϫ80°C and for use were dissolved in distilled water.…”

“…Inositol phosphoglycans (IPGs) are broadly divided into two families by separation on Amberlite columns, the IPG-P (eluting at pH 2.0) activates PDP, and the IPG-A (eluting at pH 1.3) acts upon cAMP-linked enzymes and activates acetyl-CoA carboxylase; their wide range of activities has been extensively reviewed (13)(14)(15)(16)(17)(18)(19). There is a fall in the tissue content, serum levels, and excretion of IPG-P and shifts in the IPG-P/IPG-A quotient in human diabetes type 2 and in experimental diabetes (20 -23).…”

“…In addition, adaptive changes due to altered hormonal or dietary states, such as diabetes, starvation, or high fat/high carbohydrate diets, and related changes in the expression of isoforms of PDK and PDP in a tissue-specific manner regulate the phosphorylation state of the PDC (2, 7-12). The profile of the regulation of PDK1-4 to activation by NADH and to NADH plus acetyl CoA and ATP, together with differences in the apparent K i values for ADP, confers upon tissues individual patterns of response to alterations in metabolite profile linked to hormonal and dietary changes (2, 3, 9 -12).Inositol phosphoglycans (IPGs) are broadly divided into two families by separation on Amberlite columns, the IPG-P (eluting at pH 2.0) activates PDP, and the IPG-A (eluting at pH 1.3) acts upon cAMP-linked enzymes and activates acetyl-CoA carboxylase; their wide range of activities has been extensively reviewed (13)(14)(15)(16)(17)(18)(19). There is a fall in the tissue content, serum levels, and excretion of IPG-P and shifts in the IPG-P/IPG-A quotient in human diabetes type 2 and in experimental diabetes (20 -23).…”