title: Binding of human, porcine and bovine insulin to insulin receptors from human brain, muscle and adipocytes and to expressed recombinant alternatively spliced insulin receptor isoforms.
abstract: Previous studies have suggested that human and porcine insulin exert identical effects on blood glucose and counter-regulatory hormones but elicit different neurophysiological reactions. A major goal of the present study was to investigate whether this could be caused by different relative affinities of the insulins from different species to insulin receptors from the brain compared to other tissues. Insulin receptors isolated from human brain, muscle or adipocytes as well as from cultured cells over-expressing either of the human insulin receptor isoforms (exon 11- or exon 11 +) were immobilized to microwells coated with monoclonal anti-insulin receptor antibody. Subsequently the binding of human, porcine and bovine insulin was measured. While the receptors derived from the different tissues had different affinities for insulin, there were no tissue-specific differences in the relative binding of the insulins of the three species. The insulins of the three species were also not different with regard to their binding to the receptor isoforms. Finally, in human brain homogenates no differences in the degradation rates for human, porcine and bovine insulin were detected. Thus, our data do not support the hypothesis that different neurophysiological reactions during hypoglycaemia due to human or porcine insulin are caused by differences of the binding of the insulins to human brain insulin receptors or their degradation in the human brain.
authors.affiliation: Department of Internal Medicine, University of Lübeck, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kotzke
authors.forename: M
authors.initials: M
authors.lastname: Schütt
authors.forename: U
authors.initials: U
authors.lastname: Missler
authors.forename: D E
authors.initials: DE
authors.lastname: Moller
authors.forename: H L
authors.initials: HL
authors.lastname: Fehm
authors.forename: H H
authors.initials: HH
authors.lastname: Klein
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007700:Kinetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism*; D013552:Swine; D013702:Temporal Lobe / Q000378:metabolism; D014162:Transfection
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; D011972:Receptor, Insulin