Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Robbins, D. C.
Right arrow Articles by Horton, E. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Robbins, D. C.
Right arrow Articles by Horton, E. S.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes, Vol 37, Issue 1 56-59, Copyright © 1988 by American Diabetes Association

ARTICLES

High-molecular-weight aggregates of therapeutic insulin. In vitro measurements of receptor binding and bioactivity

DC Robbins, M Hirshman, LJ Wardzala and ES Horton
Department of Medicine, University of Vermont, College of Medicine, Burlington 05405.

On the basis of a monomeric insulin standard, approximately 28% of total circulating immunoreactive insulin in insulin-dependent diabetes mellitus (IDDM) is a covalent aggregate of insulin. This aggregate probably originates in therapeutic insulin preparations. In this study, the activity of these aggregates was compared with that of monomeric insulin with regard to behavior in the radioimmunoassay, binding to insulin receptors, and biologic activity in isolated rat adipose cells. Molar activity of the aggregate in the insulin radioimmunoassay was approximately twice (240%) that of monomeric insulin, whereas the log-logit slope produced by the aggregate was indistinguishable from that of monomeric insulin. Insulin-receptor binding was determined by displacement of 125I-labeled A14-insulin by insulin or insulin aggregate (10(-10)-10(-5) M). The free-insulin and aggregate concentrations required for half-maximal displacement of 125I-insulin were 4.0 x 10(-10) and 2.25 x 10(-9) M, respectively. [1-14C]glucose incorporation into 14CO2, glyceride-glycerol, and fatty acids was measured over a wide range of insulin monomer and aggregate concentrations (0-8 nM). In the bioassay, the maximal rates of glucose metabolism were equal (normal responsiveness). However, the concentration of insulin aggregates producing half-maximal stimulation of glucose metabolism was threefold greater than that of insulin (140 vs. 46 pM, respectively), indicating decreased sensitivity of the adipose cells to the aggregates. This was associated with a sixfold decrease in the Kd for binding of aggregates to adipose cell insulin receptors compared with binding of monomeric insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 1988 by the American Diabetes Association.