The sulphonylurea drug, glimepiride, stimulates release of glycosylphosphatidylinositol-anchored plasma-membrane proteins from 3T3 adipocytes

摘要: Sulphonylurea drugs stimulate glucose transport and metabolism in muscle fat cells vitro. The molecular basis for the insulin-mimetic extrapancreatic effects of these oral antidiabetic therapeutic agents is unknown at present. Here we demonstrate that incubation 3T3 adipocytes with novel sulphonylurea, glimepiride, causes a time- concentration-dependent release glycosylphosphatidylinositol (GPI)-anchored ecto-proteins, 5'-nucleotidase, lipoprotein lipase 62 kDa cyclic AMP (cAMP)-binding protein from plasma membrane into culture medium. change localization accompanied by conversion membrane-anchored amphiphilic proteins their soluble hydrophilic versions, as judged pulse-chase experiments Triton X-114 partitioning, appearance anti-cross-reacting determinant (CRD) immunoreactivity released shown Western blotting. Metabolic labelling myo-[14C]inositol demonstrates inositol retained major portion cAMP-binding ectoprotein. identification phosphate after deamination nitrous acid suggests cleavage GPI anchor GPI-specific phospholipase C. However, longer glimepiride amount versions GPI-proteins lacking anti-CRD increases, which may be caused additional drug-stimulated hydrolytic events within structure or C-termini. Since insulin also stimulates GPI-modified proteins, combination synergistic manner, sulphonylurea exert peripheral actions adipose tissue using (part of) postreceptor signalling cascade step activation