Stimulation of a glycosyl-phosphatidylinositol-specific phospholipase by insulin and the sulfonylurea, glimepiride, in rat adipocytes depends on increased glucose transport
Abstract. Lipoprotein lipase (LPL) and glycolipidanchored cAMP-binding ectoprotein (Gcel) are modified by glycosyl-phosphatidylinositol (GPI) in rat adipocytes, however, the linkage is potentially unstable. Incubation of the cells with either insulin (0.1-30 nM) or the sulfonylurea, glimepiride (0.5-20/zM), in the presence of glucose led to conversion of up to 35 and 20%, respectively, of the total amphiphilic LPL and Gcel to their hydrophilic versions. Inositol-phosphate was retained in the residual protein-linked anchor structure. This suggests cleavage of the GPI anchors by an endogenous GPI-specific insulin- and glimepiride-inducible phospholipase (GPI-PL). Despite cleavage, hydrophilic LPL and Creel remained membrane associated and were released only if a competitor, e.g., inositol-(cyclic)monophosphate, had been added. Other constituents of the GPI anchor (glucosamine and mannose) were less efficient. This suggests reat body of information exists regarding the structural diversity as well as the biosynthesis and posttranslational attachment of glycosyl-phosphatidylinositol (GPI) ~ structures (for recent reviews see Low, 1989; McConville et al., 1993). However, the functional significance of membrane anchorage via GPI structures versus transmembrane polypeptide domains is still a matter of debate. The accessibility of GPI molecules to cleavage by phospholipase [(G)PI-PL] opens the possibility of a regu-Address all correspondence to Dr. (;tinter Miiller, Hoechst AG Frankfurt
