title: Differential binding of monoiodinated insulins to muscle and liver derived receptors and activation of the receptor kinase.
abstract: The binding affinity of monoiodoinsulin analogues to receptors purified from rat skeletal muscle and liver were compared. Insulin iodinated at tyrosine B26 bound to both muscle and liver derived insulin receptors with higher affinity than the A14-iodoisomer or native insulin. The affinity of the B26-iodoanalogue was greater for muscle than for liver derived receptors; by Scatchard analysis the affinity ratio B26/A14 was 2.8 for muscle and 1.3 for liver. The affinity of muscle and liver derived receptors for A14-iodoinsulin was not different. Dose response curves of autophosphorylation and exogenous tyrosine kinase activation showed significantly increased sensitivity to the B26-iodoanalogue (compared to the A14-iodoisomer or native insulin) in muscle derived receptors, but not in liver. The difference in affinity between muscle and liver derived insulin receptors towards B26-monoiodotyrosyl-insulin likely reflects the observed structural difference between the insulin receptor alpha-subunits from muscle and liver.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston 29425.
authors.forename: C F
authors.initials: CF
authors.lastname: Burant
authors.forename: M K
authors.initials: MK
authors.lastname: Treutelaar
authors.forename: D E
authors.initials: DE
authors.lastname: Peavy
authors.forename: B H
authors.initials: BH
authors.lastname: Frank
authors.forename: M G
authors.initials: MG
authors.lastname: Buse
mesh_terms: D000818:Animals; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: D007328:Insulin; C008147:insulin, iodo-; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin