title: Structure-function relationships of insulin receptor interactions in cultured mouse astrocytes.
abstract: Insulin receptor binding and effects upon uridine incorporation into nucleic acid were studied and compared to 3 insulin analogues, DPI, DPI-amide and DOI, in primary cultures of mouse astrocytes. From half-maximal inhibition of [125I]monoiodoinsulin binding (0.14 nM), the relative binding affinities of DPI, DPI-amide and DOI were 20%, 80% and 4% as compared with the native insulin, respectively. IC50 values were 158.5 nM for insulin, 199.5 nM for DPI-amide, 794.3 nM for DPI and 3980 nM for DOI. The corresponding relative potencies in stimulating [14C]uridine incorporation into TCA-insoluble material were 9% for DPI, 100% for DPI-amide and 1.1% for DOI. These findings are commensurate with data for these analogues in other insulin-sensitive tissues. It is concluded that the astrocyte insulin receptor has similar structural requirements to receptor in tissues outside the CNS, at least in terms of the involvement of the C-terminus of the insulin B-chain.
authors.affiliation: Department of Medicine, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Zhu
authors.forename: W
authors.initials: W
authors.lastname: Kum
authors.forename: S K
authors.initials: SK
authors.lastname: Ho
authors.forename: J D
authors.initials: JD
authors.lastname: Young
authors.forename: C S
authors.initials: CS
authors.lastname: Cockram
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001667:Binding, Competitive; D002478:Cells, Cultured; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D012313:RNA / Q000096:biosynthesis; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014529:Uridine / Q000378:metabolism
chemical_list: D007328:Insulin; D012313:RNA; D011972:Receptor, Insulin; D014529:Uridine