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
Pharmacology and Therapeutics

Lowering Plasma 1-Deoxysphingolipids Improves Neuropathy in Diabetic Rats

  1. Alaa Othman1,2,3,
  2. Roberto Bianchi4,
  3. Irina Alecu1,2,
  4. Yu Wei1,
  5. Carla Porretta-Serapiglia4,
  6. Raffaella Lombardi4,
  7. Alessia Chiorazzi5,
  8. Cristina Meregalli5,
  9. Norberto Oggioni5,
  10. Guido Cavaletti5,
  11. Giuseppe Lauria4,
  12. Arnold von Eckardstein1,2,3 and
  13. Thorsten Hornemann1,2,3⇑
  1. 1Institute for Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland
  2. 2Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
  3. 3Competence Centre for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
  4. 4Neuroalgology and Headache Unit, IRCCS Foundation, Carlo Besta Neurological Institute, Milan, Italy
  5. 5Experimental Neurology Unit and Milan Center for Neuroscience, Department of Surgery and Translational Medicine, University of Milan-Bicocca, Milan, Italy
  1. Corresponding author: Thorsten Hornemann, thorsten.hornemann{at}usz.ch.
  1. A.O. and R.B. contributed equally to this study.

Diabetes 2015 Mar; 64(3): 1035-1045. https://doi.org/10.2337/db14-1325
PreviousNext
  • Article
  • Figures & Tables
  • Suppl Material
  • Info & Metrics
  • PDF
Loading

Article Figures & Tables

Figures

  • Figure 1
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 1

    Schematic diagram showing the flow of the experiment. For the preventive schedule, a serine-enriched (Ser) or a standard diet (Std) was given from day 0 after STZ injection and the animals were followed for 18 weeks until they were killed. For the therapeutic schedule, animals received an initial standard diet for 8 weeks after STZ injection, followed by random separation into either a serine-enriched or a standard diet group. The animals then were followed until the end of the study period at week 24 after STZ.

  • Figure 2
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 2

    Effect of the serine-enriched diet on plasma concentrations of glucose, TGs, and serine. Line plots show the time course concentrations of plasma glucose (A and B), TGs (D and E), and serine (G and H) of the animals used in the study in the preventive (left) and therapeutic schedules (middle) for the different groups. Scatter plots show the values of plasma glucose (C), TGs (F), and serine (I) at week 16 after STZ injection for the preventive group and week 24 after STZ injection for the therapeutic group. The values are expressed as mean ± SEM. P values were calculated using ANOVA followed by Bonferroni correction. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. CTRL Ser, control rats on serine diet; CTRL Std, control rats on standard diet; STZ Ser, STZ rats on serine diet; STZ Std, STZ rats on standard diet.

  • Figure 3
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 3

    Effect of serine-enriched diet on plasma concentrations of typical sphingolipids. Line plots show the plasma concentrations of C18SO (A and B), C18SA (D and E), C18PhytoSO-based sphingolipids (G and H), and C18SAdiene (J and K) over the entire period of the preventive (left) and therapeutic schedules (middle) for the different groups. Scatter plots show the values for C18SO (C), C18SA (F), C18PhytoSO (I), and C18SAdiene (L) at week 17 after STZ for the preventive group and week 24 after STZ for the therapeutic groups. The values are expressed as mean ± SEM. P values were calculated using ANOVA followed by Bonferroni correction. *P < 0.05, **P < 0.01, ****P < 0.0001. CTRL Ser, control rats on serine diet; CTRL Std, control rats on standard diet; STZ Ser, STZ rats on serine diet; STZ Std, STZ rats on standard diet.

  • Figure 4
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 4

    Effect of serine-enriched diet on plasma concentrations of 1-deoxysphingolipids. Line plots show plasma concentrations of 1-deoxySA (A and B) over the entire period of the preventive (left) and therapeutic schedules (middle) for the different groups. Scatter plots show the values for 1-deoxySA (C) at week 17 after STZ for the preventive group and week 24 after STZ for the therapeutic groups. The values are expressed as mean ± SEM. P values were calculated using ANOVA followed by Bonferroni correction. ****P < 0.0001. CTRL Ser, control rats on serine diet; CTRL Std, control rats on standard diet; STZ Ser, STZ rats on serine diet; STZ Std, STZ rats on standard diet.

  • Figure 5
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 5

    Effect of L-serine on of mechanical and thermal nociception. Force withdrawal threshold (A and B) and thermal response latency (D and E) were assessed for the preventive and the therapeutic groups at the beginning of the study and over time until the end the study. Black arrows refer to the time when the serine-enriched diet was introduced to the respective groups in the therapeutic schedule. Scatter plots show the force withdrawal threshold (C) and thermal response latency (F) for the preventive groups at week 14 after STZ injection and week 23 after STZ injection for the therapeutic groups. The values are expressed as mean ± SEM. P values were calculated using ANOVA followed by Bonferroni correction. For the force withdrawal threshold, the values were log-transformed before the P values were calculated. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. CTRL Ser, control rats on serine diet; CTRL Std, control rats on standard diet; STZ Ser, STZ rats on serine diet; STZ Std, STZ rats on standard diet.

  • Figure 6
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 6

    Effect of serine on sensory NCV (A), Na+K+-ATPase activity (B), and IENF density (C). Scatter plots for the preventive (week 14 after STZ injection) and the therapeutic groups (week 23 after STZ injection). The values are expressed as mean ± SEM. P values were calculated using ANOVA followed by Bonferroni correction. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. CTRL Std, control rats on standard diet; CTRL Ser, control rats on serine diet; STZ Std, STZ rats on standard diet; STZ Ser, STZ rats on serine diet. D: Scatter plot showing the correlation between NCV and plasma 1-deoxySA concentrations. A highly significant inverse correlation between plasma 1-deoxySA concentrations and NCV was observed of the whole group of animals (P = 5.23 × 10−12). Variables were log-transformed because the control groups skewed the normal distribution to the right. Pearson correlation coefficient and the asymptomatic P value are shown.

  • Figure 7
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 7

    Effect of serine-enriched diet on axon, nerve fiber diameter. Distribution of axon (A and B) and nerve fiber diameters (C and D) shows a significant difference between the control and STZ rats (more axons and fibers with large diameters and fewer with shorter diameters in the control group). There is a significant improvement in the serine-supplemented STZ rats [STZ Ser] in the preventive group but not the therapeutic group (more axons and fibers with larger diameters and fewer with smaller diameters compared with the STZ rats on the standard diet [STZ Std]). Scatter plots show the mean ± SEM for the frequency distribution of axons or nerve fibers (three replicates from each rat and three rats per group). The solid lines represent the fitted Gaussian distribution model. Nerve fiber diameter shows two Gaussian peaks in the control rats, denoting two different fiber types; this pattern is lost in the STZ rats. P values were calculated comparing the fitted Gaussian distribution of each group. CTRL Std, control rats on standard diet.

  • Figure 8
    • Download figure
    • Open in new tab
    • Download powerpoint
    Figure 8

    Effect of a serine-enriched diet on the morphometry of DRG neurons in the preventive group. A: Light microcopy of sections of DRG neurons in the preventive group stained with toluidine blue. DRG neurons of STZ-treated animals are smaller in size compared with control animals. No evidence of cell damage was observed. Column plots show the average size of soma (B), nuclei (C), and nucleoli (D) of DRG neurons in the control (CTRL) and STZ rats on a standard diet (Std) and a serine diet (Ser). The values are expressed as mean ± SD. P values were calculated using ANOVA followed by the Tukey post hoc test. **P < 0.01, ***P < 0.001.

PreviousNext
Back to top
Diabetes: 64 (3)

In this Issue

March 2015, 64(3)
  • 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)
Print
Download PDF
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.
Lowering Plasma 1-Deoxysphingolipids Improves Neuropathy in Diabetic Rats
(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
Lowering Plasma 1-Deoxysphingolipids Improves Neuropathy in Diabetic Rats
Alaa Othman, Roberto Bianchi, Irina Alecu, Yu Wei, Carla Porretta-Serapiglia, Raffaella Lombardi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Guido Cavaletti, Giuseppe Lauria, Arnold von Eckardstein, Thorsten Hornemann
Diabetes Mar 2015, 64 (3) 1035-1045; DOI: 10.2337/db14-1325

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

Lowering Plasma 1-Deoxysphingolipids Improves Neuropathy in Diabetic Rats
Alaa Othman, Roberto Bianchi, Irina Alecu, Yu Wei, Carla Porretta-Serapiglia, Raffaella Lombardi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Guido Cavaletti, Giuseppe Lauria, Arnold von Eckardstein, Thorsten Hornemann
Diabetes Mar 2015, 64 (3) 1035-1045; DOI: 10.2337/db14-1325
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

  • Dapagliflozin Suppresses ER Stress and Improves Subclinical Myocardial Function in Diabetes: From Bedside to Bench
  • Anti-Insulin Receptor Antibodies Improve Hyperglycemia in a Mouse Model of Human Insulin Receptoropathy
  • Effect of Intensive Glycemic and Blood Pressure Control on QT Prolongation in Diabetes: The ACCORD Trial
Show more Pharmacology and Therapeutics

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.