Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Original Contributions

Kinetic Modeling of Insulin Binding to Receptors and Degradation In Vivo in the Rabbit

  1. Mones Berman,
  2. Elizabeth A McGuire,
  3. Jesse Roth and
  4. Anthony J Zeleznik
  1. Laboratory of Theoretical Biology, Division of Cancer Biology and Diagnosis, National Cancer Institute, and Diabetes Branch, NIAMDD, National Institutes of Health Bethesda, Maryland
  1. Address reprint requests to Mones Berman, Ph.D., Laboratory of Theoretical Biology, NCI, 9000 Rockville Pike, Bethesda, Maryland 20205.
Diabetes 1980 Jan; 29(1): 50-59. https://doi.org/10.2337/diab.29.1.50
PreviousNext
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

In vivo metabolism of insulin, with emphasis on the distribution, binding, and degradation from receptor and nonreceptor sites, has been studied in rabbits by analyzing the kinetics of antibody-bindable, TCA-precipitable, and TCA-soluble components in plasma. Tracer amounts of 125I-and 131I-labeled high affinity (pork) and low affinity (guinea pig) insulins were injected simultaneously into rabbits in the basal state or after a large bolus of unlabeled pork insulin. In one series of experiments, a bolus of unlabeled pork insulin was given from 5 to 30 min after the tracers. Based on the kinetic curves derived in these experiments, a model is developed for insulin metabolic pathways in vivo. A number of features are contained in the model. First, some of the kinetics are caused by distribution spaces in the body and some by specific binding sites, presumably receptors. Two equilibration phases between plasma insulin and receptors can be detected. The first and major one occurs within about one minute. The second one takes about 15 or 20 min. Partial degradation of the insulin molecule can be detected rapidly by the kinetics and is associated with the rapid (1 min) receptor phase. About 27% of the labeled insulin molecules are partially degraded via this pathway. There is, also, irreversible loss of insulin from the receptors without significant return of label to plasma during the experiment. This loss could be a result of internalization of insulin by the cells. About 48% of the insulin injected follows this pathway. The remaining degradation of insulin (∼24%) takes place at other sites in the body. The results of the kinetic analysis also suggest that there are two populations of receptors. The high affinity population has an equilibrium dissociation constant equal to about 9 × 10−9 M, a value comparable to that observed in vitro (∼5 × 10−9 M). The low affinity population has an equilibrium dissociation constant about 100 times greater than that of the high affinity population; its capacity, however, is about 30 times greater. It is, further, concluded that the TCA-soluble degradation products observed in plasma could not be accounted for by the partial and irreversible degradation pathways identified in the insulin model. They could be accounted for, however, by a 5%–15% subpopulation of injected labeled TCA-precipitable molecules that decay monoexponentially from plasma.

  • Received June 14, 1979.
  • Copyright © 1980 by the American Diabetes Association

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this Issue

January 1980, 29(1)
  • Table of Contents
  • Index by Author
Sign up to receive current issue alerts
View Selected Citations (0)
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Kinetic Modeling of Insulin Binding to Receptors and Degradation In Vivo in the Rabbit
(Your Name) has forwarded a page to you from Diabetes
(Your Name) thought you would like to see this page from the Diabetes web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Kinetic Modeling of Insulin Binding to Receptors and Degradation In Vivo in the Rabbit
Mones Berman, Elizabeth A McGuire, Jesse Roth, Anthony J Zeleznik
Diabetes Jan 1980, 29 (1) 50-59; DOI: 10.2337/diab.29.1.50

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Kinetic Modeling of Insulin Binding to Receptors and Degradation In Vivo in the Rabbit
Mones Berman, Elizabeth A McGuire, Jesse Roth, Anthony J Zeleznik
Diabetes Jan 1980, 29 (1) 50-59; DOI: 10.2337/diab.29.1.50
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Effect of Hyperketonemia and Hyperlacticacidemia on Symptoms, Cognitive Dysfunction, and Counterregulatory Hormone Responses During Hypoglycemia in Normal Humans
  • HLA-DQ-Restricted, Islet-Specific T-Cell Clones of a Type I Diabetic Patient: T-Cell Receptor Sequence Similarities to Insulitis-Inducing T-Cells of Nonobese Diabetic Mice
  • STZ Transport and Cytotoxicity: Specific Enhancement in GLUT2-Expressing Cells
Show more Original Contributions

Similar Articles

Navigate

  • Current Issue
  • Online Ahead of Print
  • Scientific Sessions Abstracts
  • Collections
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes Care
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.