ISSN:
1432-0428
Keywords:
Receptor-binding assay of insulin
;
insulin receptor
;
plasma membrane
;
insulin derivatives
;
chemically modified insulins
;
biological activity in vitro and in vivo
;
insulin structure-function relationships
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The binding affinity for the insulin receptor was determined with a variety of insulin derivatives and compared to the biological activity in vitro and in vivo and to the physical properties of the derivatives. The relative binding affinity of each derivative was measured in a specific insulin-receptor binding system using mono 125I-insulin and purified plasma membranes of rat liver. Twenty one chemically modified insulins were investigated, including acetylinsulins, crosslinked insulin dimer and insulin trimer, and insulins with an A1-B1 or A1-B29 intra-molecular crosslink. The relative binding affinity corresponded to the relative biological potency in vitro for all of the derivatives studied. There was a good agreement between the activity in vitro and the physical properties as measured by circular dichroism spectroscopy with the acetylinsulins and with the crosslinked insulin monomer, dimer and trimer. In contrast, with most of the derivatives possessing an intra-molecular crosslink, the very reduced binding affinity (0.2–5.9%) and the comparably reduced biological potency in vitro opposed the moderate changes in physical properties. Biological activity was consistently higher in vivo than in vitro.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00421406
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