Phosphoinositides and metabolic control: how many messengers?

A defect in sodium-dependent amino acid uptake in diabetic rabbit peripheral nerve. Correction by an aldose reductase inhibitor or myo-inositol administration.

“…In any case, both sodium-dependent AIB uptake and sodium-potassium ATPase activity appear to be reduced in diabetic nerve as a result of underlying MI depletion. These two defects may be linked serially or in parallel, and may involve one or more metabolic pools of MI, and/or distinct but phosphoinositide-related processes (39). All of these possibilities imply that metabolism ofa specific MI pool or pools rather than the total tissue MI content mediate some of the effects of MI depletion and repletion on nerve metabolism such as the defect in system A amino transport, as has been suggested by Winegrad and his colleagues (8,26).…”

“…The known relationship(s) between phosphoinositide signaling and membrane transport are widespread and complex, involving highly regulated inositol-1,4,5-trisphosphate-and inositol-1,4,5-tetrakisphosphate-mediated intracellular (40, 41) and transplasmalemmal (40) calcium fluxes, and diacyl-glycerol-mediated stimulation of phospholipid-and-calcium-dependent protein kinase C (39). Protein kinase C agonists affect growth and differentiation in some cells, and have multiple effects on membrane transport such as the induction of the glucose transporter gene (42).…”

“…MI regulates intracellular metabolism primarily through its incorporation into inositol-containing membrane phospholipids that serve as precursors for phospholipase-C-generated inositol-phosphate and diacylglycerol second messengers (39). The known relationship(s) between phosphoinositide signaling and membrane transport are widespread and complex, involving highly regulated inositol-1,4,5-trisphosphate-and inositol-1,4,5-tetrakisphosphate-mediated intracellular (40, 41) and transplasmalemmal (40) calcium fluxes, and diacyl-glycerol-mediated stimulation of phospholipid-and-calcium-dependent protein kinase C (39).…”

Recent advances in the chemistry and biochemistry of inositol phosphates of biological interest

“…This was originally stimulated by a seminal review of Mi~he11.~~* The historical development of the 'Phospholipid Effect' and its relevance to current research has been reviewed. 10* 54,55 Phospholipase C (for PIP2)…”