Immunoreactivity and biologic activity of semisynthetic [LeuB-30]-insulin: potential value in the treatment of insulin antibody-mediated insulin resistance.
Insulin analogues with different amino acids, including threonine, alanine, L-leucine, D-leucine, L-leucine amide, phenylalanine, tri-alanine, or desalanine, at the B-30 position were semisynthesized from pork insulin by the new enzymatic method. The order of ability of the insulin analogues to bind to anti-insulin sera was [AlaB-30] greater than desalanine greater than [ThrB-30] greater than [Ala-Ala-AlaB-30] greater than [D-LeuB-30], [Leu-NH2B-30],[PheB-30] greater than desoctapeptide greater than or equal to [LeuB-30]. The ability of insulin analogues with different amino acids at B-30 to bind to receptors, as well as their biologic potency tested with glucose uptake in isolated rat adipocytes, was comparable among the analogues. These results suggest that [LeuB-30]-insulin demonstrated the least immunoreactivity and has full activity in receptor binding and biologic effect, and that it may be useful for treatment of anti-insulin antibody-mediated insulin resistance.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000936:Antigen-Antibody Complex; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D007330:Insulin Antibodies; D007333:Insulin Resistance; D007700:Kinetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D013329:Structure-Activity Relationship
D000936:Antigen-Antibody Complex; D001786:Blood Glucose; D007328:Insulin; D007330:Insulin Antibodies; C030314:insulin, Leu(B30)-; D003847:Deoxyglucose; D011972:Receptor, Insulin