Regulation and function of an insulin-sensitive glycosyl-phosphatidylinositol during T lymphocyte activation

Asymmetric distribution of the phosphatidylinositol‐linked phospho‐oligosaccharide that mimics insulin action in the plasma membrane

“…In a variety of cells including murine myocytes BC3H1 [l], H35 hepatoma cells [2], T lymphocytes [3] and rat hepatocytes [4], insulin promotes the phosphodiesteratic hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) and thus releases and increases the intracellular levels of the polar headgroup of this lipid. This polar headgroup, a phosphooligosaccharide containing inositol, glucosamine, galactose and phosphate [I, 2, 5, 61, mimics insulin-directed effects on protein phosphorylation/dephosphorylation [7], as well as a variety of the biological effects of this hormone, including lipolysis [8], lipogenesis [9] and the effects of the hormone on pyruvate kinase, glycogen phosphorylase and cyclic AMP levels [lo].…”

Insulin induces a similar reduction in the concentrations of its own receptor and of an insulin‐sensitive glycosyl‐phosphatidylinositol in isolated rat hepatocytes

“…The magnitude of the diminution of GPI levels and insulin receptor number were dependent on the concentrations of insulin, with a correlation coefficient of I*= 0.72 and r= 0.77, respectively. Reduction of insulin binding and of glycosyl-PI occur within the first hour of preincubation with insulin ( fig.2) and then remam decreased for up to 6 h of preincubation, A correlation between the levels of glycosyl-PI and the induction of insulm receptors has also been observed in T lymphocytes [16]. Similarly, in CHO cells bearmg normal human insulin receptors, the levels of glycosyl-PI are 3-fold higher than in the parental cells and in cells bearing a mutant receptor that lacks tyrosine kinase activity [ 171.…”

“…Glycosyl-PI molecules are considered as precursors to signal transduction elements since treatment of isolated hepatocytes with physiological concentrations of insulin Initiated the rapid loss and resynthesis of glycosyl-PI and the appearance of its polar head-group through the action of a PI-specific phospholipase C [2, 3,16]. This polar head group has been reported to mimic insulin action, modulating cyclic AMP phosphodiesterase, pyruvate dehydrogen~e and adenylate cyclase in cell extracts [18], through its effects on pyruvate kinase and glycogen phosphorylase in rat hepatocytes [19] and in its ability to copy the antilipolytic [20] and lipogenic [21] effects of insulin and the effects of this hormone on protein phosphorylatron/ dephosphorylatron [.5,22] and on phospholiprd methyltransferase 1231.…”

Does oligosaccharide‐phosphatidylinositol (glycosyl‐phosphatidylinositol) hydrolysis mediate prolactin signal transduction in granulosa cells?

“…Granulosa cells were labelled with putative precursors and (Ose),,PtdIns isolated by chromatography in the acid and basic mobile phases described (Gaulton et a1 , 1988;Mato et al, 1988aMato et al, , 1988b and further characterized by acid hydrolysis, bacterial PLC treatment and nitrous acid deamination ( Table 2). The isotopic integrity after metabolic labelling was evaluated by TLC analysis of an acid hydrolysate of the putative ['H](Ose),PtdIns (Mato et al, 1987a;Gaulton et al, 1988). No radioactivity was detected in (Ose),,PtdIns when granulosa cells were incubated with -vine 7-globulin as standard.…”