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
Obesity Studies

Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity

  1. Jessica L. Cote1,
  2. Lawrence S. Argetsinger2,
  3. Anabel Flores3,
  4. Alan C. Rupp4,
  5. Joel M. Cline2,
  6. Lauren C. DeSantis2,
  7. Alexander H. Bedard2,
  8. Devika P. Bagchi2,
  9. Paul B. Vander2,
  10. Abrielle M. Cacciaglia2,
  11. Erik S. Clutter2,
  12. Gowri Chandrashekar2,
  13. Ormond A. MacDougald2,3,4,
  14. Martin G. Myers Jr.1,2,3,4 and
  15. Christin Carter-Su1,2,3,4⇑
  1. 1Neuroscience Program, University of Michigan Medical School, Ann Arbor, MI
  2. 2Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI
  3. 3Cell and Molecular Biology Program, University of Michigan Medical School, Ann Arbor, MI
  4. 4Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
  1. Corresponding author: Christin Carter-Su, cartersu{at}med.umich.edu
Diabetes 2021 Feb; 70(2): 400-414. https://doi.org/10.2337/db20-0687
PreviousNext
  • Article
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF
Loading

Abstract

Mice lacking SH2B1 and humans with variants of SH2B1 display severe obesity and insulin resistance. SH2B1 is an adapter protein that is recruited to the receptors of multiple hormones and neurotrophic factors. Of the four known alternatively spliced SH2B1 isoforms, SH2B1β and SH2B1γ exhibit ubiquitous expression, whereas SH2B1α and SH2B1δ are essentially restricted to the brain. To understand the roles for SH2B1α and SH2B1δ in energy balance and glucose metabolism, we generated mice lacking these brain-specific isoforms (αδ knockout [αδKO] mice). αδKO mice exhibit decreased food intake, protection from weight gain on standard and high-fat diets, and an adiposity-dependent improvement in glucose homeostasis. SH2B1 has been suggested to impact energy balance via the modulation of leptin action. However, αδKO mice exhibit leptin sensitivity that is similar to that of wild-type mice by multiple measures. Thus, decreasing the abundance of SH2B1α and/or SH2B1δ relative to the other SH2B1 isoforms likely shifts energy balance toward a lean phenotype via a primarily leptin-independent mechanism. Our findings suggest that the different alternatively spliced isoforms of SH2B1 perform different functions in vivo.

Footnotes

  • This article contains supplementary material online at https://doi.org/10.2337/figshare.13229090.

  • Received June 30, 2020.
  • Accepted November 12, 2020.
  • © 2020 by the American Diabetes Association
https://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.

View Full Text

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
Diabetes: 70 (2)

In this Issue

February 2021, 70(2)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author
  • Masthead (PDF)
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.
Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity
(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
Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity
Jessica L. Cote, Lawrence S. Argetsinger, Anabel Flores, Alan C. Rupp, Joel M. Cline, Lauren C. DeSantis, Alexander H. Bedard, Devika P. Bagchi, Paul B. Vander, Abrielle M. Cacciaglia, Erik S. Clutter, Gowri Chandrashekar, Ormond A. MacDougald, Martin G. Myers, Christin Carter-Su
Diabetes Feb 2021, 70 (2) 400-414; DOI: 10.2337/db20-0687

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

Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity
Jessica L. Cote, Lawrence S. Argetsinger, Anabel Flores, Alan C. Rupp, Joel M. Cline, Lauren C. DeSantis, Alexander H. Bedard, Devika P. Bagchi, Paul B. Vander, Abrielle M. Cacciaglia, Erik S. Clutter, Gowri Chandrashekar, Ormond A. MacDougald, Martin G. Myers, Christin Carter-Su
Diabetes Feb 2021, 70 (2) 400-414; DOI: 10.2337/db20-0687
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
    • Abstract
    • Introduction
    • Research Design and Methods
    • Results
    • Discussion
    • Article Information
    • Footnotes
    • References
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Defective FXR-SHP Regulation in Obesity Aberrantly Increases miR-802 Expression, Promoting Insulin Resistance and Fatty Liver
  • Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed a High-Fat Diet
  • Placental Insulin/IGF-1 Signaling, PGC-1α, and Inflammatory Pathways Are Associated With Metabolic Outcomes at 4–6 Years of Age: The ECHO Healthy Start Cohort
Show more Obesity Studies

Similar Articles

Subjects

  • Obesity-Animal

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.